Summary of the effect of phenolic acids on skeletal muscle glucose transport.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"3138",leadTitle:null,fullTitle:"Biomass Now - Cultivation and Utilization",title:"Biomass Now",subtitle:"Cultivation and Utilization",reviewType:"peer-reviewed",abstract:"This two-volume book on biomass is a reflection of the increase in biomass related research and applications, driven by overall higher interest in sustainable energy and food sources, by increased awareness of potentials and pitfalls of using biomass for energy, by the concerns for food supply and by multitude of potential biomass uses as a source material in organic chemistry, bringing in the concept of bio-refinery. 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Diabetes is one of the most rapidly increasing chronic diseases in the world. According to the International Diabetes Federation [1], there are now 415 million adults aged 20–79 with diabetes worldwide, and there will be 642 million people living with the disease by 2040. Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, which is due primarily to lifestyle factors and genetics. Numerous lifestyle factors, including excessive caloric intake, physical inactivity, cigarette smoking, and generous consumption of alcohol, are considered to be important to the development of T2DM [2]. T2DM care is usually managed by a multidisciplinary healthcare approach, which includes a combination of dietary restriction, exercise, hypoglycemic agents, and/or insulin. In present times, evidences show a commonness of utilization of alternative medicines for the treatment of T2DM.
\n\nA traditional herbal medicine, also called as phytomedicine, has been used since ancient time in many regions in the world. Phytomedicine is a medicine mainly derived from whole leaves, roots, stems, and plant extracts for promoting health and treating illness [3]. Plants produce numerous diversity of chemicals known as secondary metabolites through evolved secondary biochemical pathways. These secondary metabolites serve as defense compounds against herbivores or infection and thereby enhance their ability to survive. These compounds are also helpful for humans to protect themselves against diseases and are called phytochemical. Each type of fruit or vegetable contain hundreds of phytochemical, and these phytochemicals exhibit multiple beneficial effects in the treatment of T2DM [4].
\nChemical structures of benzoic acid and cinnamic acid derivatives.
Phenolic acids, which are part of the secondary metabolites, belong to the family of phenolic compounds and are the most common compounds in non-flavonoid group. Phenolic acids are synthesized from the shikimic acid pathway from L-phenylalanine or L-tyrosine [5]. These compounds exist predominantly as hydroxybenzoic acids, which include gallic acid, salicylic acid, protocatechuic acid, vanillic acid, and gentisic acid and hydroxycinnamic acids, which include
Because skeletal muscle is responsible for approximately 80% of insulin-mediated glucose utilization [9], it is considered that defects in insulin action on skeletal muscle are key contributors to the pathophysiology of T2DM. Studies have shown that several phenolic acids have antidiabetic effects [8], and these compounds have been implicated in the regulation of skeletal muscle glucose metabolism, especially glucose transport, a rate-limiting step for glucose utilization. However, the precise mechanism of how phenolic acids modulate glucose transport has not been firmly established. In this chapter, we provide recent experimental evidences linking phenolic acids to glucose transport and upstream signaling pathways in skeletal muscle.
\n\nGlucose transport is a major regulatory step for whole-body glucose disposal that occurs by a system of facilitated diffusion with glucose transporter (GLUT)-mediated process. GLUT is a protein of ∼500 amino acids and is predicted to possess 12 transmembrane-spanning alpha helices and a single N-linked oligosaccharide. GLUT1, 3, 4, 5, 8, 10, 11, and 12 exist in mammalian skeletal muscle tissue, and especially, GLUT4 is the predominant glucose transporter isoform present in skeletal muscle. GLUT4 is present in intracellular vesicular pool in the basal non-stimulated state, and the translocation of GLUT4 from an intracellular location to the plasma membrane and T-tubules is a major determinant of acute regulation of glucose transport [10] (Figure 2). These glucose transport processes are regulated mainly through two different systems: insulin-dependent and insulin-independent mechanism.
\n\nInsulin is a peptide hormone produced by β cells of the pancreatic islets. Insulin consists of two polypeptide chains, the A and B chains, linked together by disulfide bonds. It is first synthesized as a single polypeptide called preproinsulin in pancreatic β-cells, and then it is cleaved to form a smaller protein, proinsulin. The conversion of proinsulin to insulin occurs through the combined action of the prohormone convertases [12].
\nThe insulin receptor is a member of the ligand-activated receptor and tyrosine kinase family of transmembrane-signaling proteins that consists of two extracellular α subunits and two transmembrane β subunits connected by disulfide bridges [13]. Binding of insulin to the extracellular domain of the insulin receptor α subunit triggers tyrosine phosphorylation of the intracellular domain of the β subunit [14]. Following the autophosphorylation of the receptor, the insulin receptor phosphorylates insulin receptor substrate (IRS)-1 on tyrosine residues. Tyrosine-phosphorylated IRS then binds to the Src homology 2 (SH2) domain-containing adaptor protein p85, a regulatory subunit of phosphatidylinositol-3 kinase (PI3K), resulting in activation of the catalytic p110 subunit of PI3K. This results in the generation of the critical second messenger PI3,4,5-triphosphate, which in turn triggers the activation of Akt. Recently, TBC1 domain family (TBC1D) member 1 (TBC1D1) and member 4 (TBC1D4) have been suggested to act as downstream mediators of Akt. TBC1D1 and TBC1D4 contain Rab GTPase-activating protein (GAP) domains that prevent GLUT4 translocation by inactivating Rab proteins. TBC1D1 and TBC1D4 dissociate from GLUT4 vesicles in the phosphorylated state and thereby facilitate GLUT4 translocation and glucose transport [15, 16] (Figure 2).
\nMolecular mechanism of stimulating insulin-dependent and insulin-independent glucose transport in skeletal muscle. This figure was adapted from Egawa et al. [
A serine/threonine protein kinase, 5′AMP-activated protein kinase (AMPK), is critical for insulin-independent glucose transport in the muscle through translocation of GLUT4. AMPK comprises a catalytic α subunit and the regulatory subunits β and γ [17] in a total of 12 possible heterotrimeric combinations of two α, two β, and three γ subunits [18]. In skeletal muscle, the predominant heterotrimeric complexes include α1/β2/γ1, α2/β2/γ1, and α2/β2/γ3 [19]. The α subunit has a catalytic domain that contains the activating phosphorylation site (Thr172) at the N-terminus, an auto-inhibitory domain, and a conserved C-terminal domain that interacts with β and γ subunits [20–24]. There are two distinct α isoforms (α1 and α2): α1 is expressed ubiquitously, whereas α2 is dominant in the skeletal muscle, heart, and liver [25]. The regulatory β subunit contains a C-terminal region that interacts with α and γ subunits and a central region that binds glycogen [26]. The regulatory γ subunit contains binding sites of adenine nucleotides (adenosine monophosphate (AMP), adenosine diphosphate (ADP), or adenosine triphosphate (ATP)) [18].
\nAMPK typically works as a signaling intermediary in muscle cells by monitoring cellular energy status, such as AMP/ATP ratio and creatine/creatine phosphate (PCr) ratio [17]. Binding of AMP to the Bateman domains of the AMPK γ subunit leads the allosteric activation of AMPK and phosphorylation of the Thr172 residue of the α subunit, which is crucial for maximal kinase activity. The level of phosphorylation also depends on the balance of activities of upstream kinases including liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) and protein phosphatases [24, 27]. The LKB1 complex is constitutively active but is not activated directly by AMP. The binding of AMP to AMPK induces a structural change that assists phosphorylation of AMPK by the LKB1 complex [28, 29]. On the other hand, CaMKK activates AMPK in response to increased intracellular Ca2+ levels independently of energy status [30–32].
\nAMPK is also activated without energy depletion by 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR), a pharmacological activator of AMPK. When taken up into skeletal muscle, AICAR is converted by adenosine kinase to ZMP, a monophosphorylated derivative that mimics the effects of AMP on AMPK [17]. AICAR-induced activation of AMPK leads to insulin-independent stimulation of glucose transport in skeletal muscle [33, 34] accompanied by GLUT4 translocation to the plasma membrane [35]. Moreover, AICAR-stimulated glucose transport is abrogated completely in muscles from mice with muscle-specific expression of a dominant-negative (kinase dead) form of AMPK [36], indicating that increased AMPK activity is sufficient for the stimulation of glucose transport in skeletal muscle.
\nAICAR-stimulated glucose transport is not inhibited by a PI3K inhibitor wortmannin [33], and the increase in glucose transport induced by the combination of maximal AICAR and maximal insulin stimulation is partly additive [33]. Therefore, the underlying molecular signaling mechanisms regulating insulin-dependent and insulin-independent glucose transport have been considered to be distinct. In this regard, recent studies have revealed that AMPK promotes GLUT4 translocation likely through TBC1D1 and TCB1D4 [37]. In short, insulin-dependent and insulin-independent signaling of glucose transport systems seem to convergence at TBC1D1 and TBC1D4 (Figure 2).
\nCaffeic acid (3,4-dihydroxycinnamic acid) is the most frequently studied phenolic acids in diabetes research. A prospective investigation conducted in two cohorts of US women demonstrated that there was an inverse association between urinary excretion level of caffeic acid and T2DM risk [38], indicating that dietary intake of caffeic acid may alleviate a development of T2DM. Indeed, several studies have shown the hypoglycemic action of caffeic acid. Intravenous injection of caffeic acid (0.5–5 mg/kg) into both streptozotocin (STZ)-induced diabetic rats and rats with insulin resistance exhibited an acute (<30 min) effect of lowering plasma glucose in a dose-dependent manner [39, 40]. Further, chronic (5–12 weeks) dietary supplementation with caffeic acid (0.02–2%) lowered blood glucose level in diabetic mice [41–43].
\nA previous work by us first demonstrated that incubation of isolated rat skeletal muscles with caffeic acid (0.1–1 mM) acutely (<30 min) enhanced AMPKα Thr172 phosphorylation [44, 45] (Figure 3). Phosphorylation of acetyl-CoA carboxylase (ACC) Ser79 exhibited parallel changes to AMPK phosphorylation. ACC is a major substrate of AMPK in skeletal muscle, and phosphorylation of ACC at Ser79 reflects the total AMPK activity [46–48]. Correspondingly, caffeic acid (1 mM, 30 min) stimulated insulin-independent glucose transport in skeletal muscle (Figure 4). Other researchers also have shown that caffeic acid enhanced insulin-independent glucose transport in isolated adipocytes [39] and cultured muscle cells [40]. Therefore, the stimulatory effect of caffeic acid on insulin-independent glucose transport may contribute to the hypoglycemic action, partly through AMPK-mediated mechanism.
\nThe effect of caffeic acid on phosphorylation status of AMPKα Thr172 in skeletal muscle. (A) Isolated epitrochlearis muscles were incubated with caffeic acid at indicated concentration for 30 min. (B) Isolated epitrochlearis muscles were incubated with caffeic acid (1 mM) at indicated time. Muscle lysates were then analyzed for phosphorylation of AMPKα Thr172 (pAMPK) by western blot analysis. Fold increases are expressed relative to the level of muscles in the non-stimulated group. Representative immunoblots are shown. Values are mean ± SE. *
The finding that caffeic acid enhances phosphorylation status of AMPKα Thr172 indicates that caffeic acid leads to covalent modification through upstream kinases. Since the binding of AMP to AMPK facilitates the phosphorylation of AMPK by the LKB1 complex [28], LKB1 is considered as a crucial AMPK kinase in response to energy depletion in skeletal muscle. When cellular ATP level is depleted, phosphate is transferred from PCr to ADP to reproduce ATP. Decreased PCr level leads to an increase in free ADP and thereby causes AMP accumulation through the reaction of adenylate kinase, and thus a reduction of PCr level indicates a cellular energy depletion. In our previous work [44], we observed that incubation of rat skeletal muscles with caffeic acid decreased PCr level, suggesting that LKB1 is a possible kinase to enhance the caffeic acid-induced AMPKα Thr172 phosphorylation.
\n\nThe effect of caffeic acid on insulin-independent glucose transport in rat skeletal muscles. Isolated epitrochlearis muscles were incubated in the absence (control) or presence of 1 mM caffeic acid for 30 min, and then glucose transport activity was measured using the glucose analog 3-O-methylglucose. Values are mean ± SE. *
Exercise (muscle contraction) is a strong stimulator for insulin-independent glucose transport. Due to the provision of energy for contracting muscle during exercise, AMP and ADP levels are rapidly increased in an intensity-dependent manner while ATP levels decline slightly. Since AMPK is a sensor of cellular energy status that is activated by AMP/ATP ratio, AMPK is activated during exercise in an intensity-dependent manner [49–52]. Thus, exercise can regulate insulin-independent glucose transport by a mechanism involving AMPK [33]. Recent work by us showed an interesting finding that muscle contraction and caffeine, which is the most widely consumed phytoactive substance in the world, synergistically stimulate insulin-independent glucose transport and AMPK Thr172 phosphorylation in skeletal muscle [45]. This result indicates the possibility that some phytochemicals enhance the maximal capacity of contraction-induced AMPK activity in skeletal muscle. In the point of view, we evaluated the effect of caffeic acid on contraction-stimulated AMPK activity in skeletal muscle. Maximal activation of AMPK by contraction was induced by 10 min tetanic contraction according to the protocol by Musi et al. [52]. AMPKα Thr172 phosphorylation was increased in response to caffeic acid (1 mM, 30 min) stimulation; however, caffeic acid had no effect on the contraction-stimulated AMPKα Thr172 phosphorylation [45]. This finding suggests that caffeic acid has no capacity for enhancing contraction-induced AMPK activity.
\nIt seems that caffeic acid stimulates insulin-dependent glucose transport at insulin resistance state in skeletal muscle. Insulin resistance is in which there are impaired biological and physiological responses to insulin in the tissue, and skeletal muscle insulin resistance is a major factor in the pathogenesis of T2DM. The underlying cellular mechanisms are yet unclear, but tumor necrosis factor α (TNFα), which is a member of the TNF ligand superfamily and a multifunctional cytokine, is implicated in the development of insulin resistance [53]. Activation of the TNF receptor results in stimulation of nuclear factor-κB (NF-κB) signaling via inhibitor κB kinase (IKK). IKK is the master regulator of NF-κB activation in response to inflammatory stimuli, and the IKK/NF-κB pathway is considered to be a core mechanism that causes insulin resistance in peripheral tissues including skeletal muscle [54, 55]. We demonstrated that, during insulin-stimulated condition, caffeine-induced insulin resistance which includes activation of IKK/NF-κB signaling and suppression of Akt Ser473 phosphorylation, which is required for the full activation of Akt, and insulin-dependent glucose transport, were alleviated by the treatment with caffeic acid in rat skeletal muscle [56]. Hence, caffeic acid may have an ability to improve insulin resistance state that is induced by activation of IKK/NF-κB signaling. Notably, caffeic acid does not stimulate insulin signaling pathway in normal state because we have shown that incubation of isolated rat skeletal muscle with caffeic acid had no effect on stimulating Akt Ser473 phosphorylation in the basal condition [44, 45].
\nChlorogenic acid is the ester of caffeic acid and (−)-quinic acid and has been implicated in reducing the risk of T2DM. In animal study, treatment of chlorogenic acid (250 mg/kg) acutely (<30 min) lowered blood glucose concentration during glucose tolerance test in diabetic db/db mice [57, 58]. Furthermore, repeated (2–12 weeks) treatment of chlorogenic acid (80–250 mg/kg/day) improved fasting blood glucose concentration, HOMA-IR index (fasting insulin [μU/ml]×fasting glucose [mmol/l]/22.5), blood glucose concentration during glucose or insulin tolerance test in db/db mice [58, 59], and high-fat diet-induced diabetic mice [60]. Intervention with lower doses of chlorogenic acid (5 mg/kg/day) also improved the peak blood glucose concentration during glucose tolerance test in Zucker (fa/fa) rats although fasting blood glucose concentration did not change [61]. In human study, chlorogenic acid ingestion (1 g) reduced blood glucose concentration during oral glucose tolerance test in overweight men [62]. Thus, the accumulated evidences strongly suggest that chlorogenic acid has a hypoglycemic effect, but the cellular mechanism of action is not fully understood yet.
\nStimulatory effect of chlorogenic acid on skeletal muscle glucose transport was firstly reported by Prabhakar and Doble [63]. They revealed that incubation with chlorogenic acid (25 μM) stimulated insulin-independent glucose transport within 3 h in differentiated L6 skeletal muscle cells. Subsequently, Ong et al. [57] demonstrated that incubation of isolated skeletal muscle from db/db mice and L6 skeletal muscle cells with chlorogenic acid (1–10 mM) for 1–24 h enhanced insulin-independent glucose transport. They also showed that chlorogenic acid-stimulated glucose transport was inhibited by the pretreatment with compound C, an AMPK inhibitor, but not wortmannin, a PI3K inhibitor. These findings suggest that chlorogenic acid stimulates skeletal muscle glucose transport via insulin-independent and AMPK-dependent mechanism.
\nThe previous work by us investigated the acute effect of chlorogenic acid on AMPKα Thr172 phosphorylation status in rat skeletal muscle [44] and showed that incubation with chlorogenic acid (<1 mM, <60 min) had no effect on AMPKα Thr172 phosphorylation in isolated rat skeletal muscle. In contrast, Ong et al. [57] demonstrated that chlorogenic acid had an ability to enhancing AMPK activity in L6 skeletal muscle cells in dose-dependent (1–10 mM) and time-dependent (1–24 h) manners. These findings suggest that chlorogenic acid directly acts skeletal muscle and stimulates AMPK, and that relatively higher concentration of chlorogenic acid (>1 mM) and/or longer stimulation period (>60 min) is needed to stimulate skeletal muscle AMPK.
\nAdiponectin is an adipokine that has been recognized as a key regulator of glucose metabolism. Binding of adiponectin to adiponectin receptor AdipoR1 induces Ca2+ influx and leads to the activation of CaMKK/AMPK signaling in skeletal muscle [64]. A study showed that AMPKα Thr172 phosphorylation and ACC Ser79 phosphorylation were upregulated in response to chronic (2 weeks) administration of chlorogenic acid (250 mg/kg/day) in skeletal muscle of db/db mice [58]. In addition, the treatment also increased CaMKK expression in skeletal muscle. More recently, Jin et al. [59] showed that treatment with chlorogenic acid (80 mg/kg/day) for 12 weeks increased AMPKα Thr172 phosphorylation as well as AdipoR1 expression in skeletal muscle of db/db mice. Collectively, chronic treatment of chlorogenic acid may act as an antidiabetic agent through stimulating adiponectin-AMPK signaling because AMPK induces a variety of metabolic changes toward antidiabetic property: promoting glucose transport [33, 34, 36, 65], GLUT4 expression [66–68], fatty acid oxidation [49, 69, 70], mitochondrial biogenesis [71, 72], insulin sensitivity [73, 74], and fiber-type shift toward the slower and more oxidative phenotype [75].
\nNotably, chlorogenic acid is hydrolyzed by intestinal microflora into various aromatic acid metabolites including caffeic and quinic acids [76]. Additionally, it is reported that absorption rate of caffeic acid in the small intestine of humans is 95% but chlorogenic acid is 33% [77]. These observations suggest that the health-promoting effects of chlorogenic acid might be attributed to the actions of chlorogenic acid-derived caffeic acid. In this context, the stimulatory effect of oral intake of chlorogenic acid as well as caffeic acid at physiological doses on AMPK activation and AMPK-related metabolic events, including glucose transport in skeletal muscle, must be confirmed.
\nGallic acid (3,4,5-trihydroxybenzoic acid) is known to have a variety of cellular functions including beneficial effects on T2DM. Chronic treatment (4–16 weeks) with gallic acid (25–100 mg/kg/day) produced significant decrease in elevated fasting serum glucose level in STZ-induced diabetic rats [78], in high-fat diet-induced diabetic mice [79], or in high-fat diet/STZ-induced diabetic rats [80, 81]. Four weeks of treatment with gallic acid (10–30 mg/kg/day) in high-fructose diet-induced diabetic rats also ameliorates hyperglycemia and HOMA-IR index and improved glucose clearance during oral glucose tolerance test [82].
\n\nA study reported that treatment with gallic acid (10 μM) for 30 min induces GLUT4 translocation and insulin-independent glucose transport in 3T3-L1 adipocytes [83]. We found that a water-soluble Pu-erh tea extract which contained 9.11% gallic acid stimulated Akt Ser473 phosphorylation in a dose- and time-dependent manner with a concomitant increase in insulin-independent glucose transport in isolated rat skeletal muscle [84]. By contract, the Pu-erh tea extract did not change the phosphorylation status of AMPKα Thr172. Correspondingly, incubation of isolated rat skeletal muscle with gallic acid (820 μM) for 30 min robustly stimulated Akt Ser473 phosphorylation without affecting AMPK phosphorylation [84] (Figure 5). These findings indicate that gallic acid stimulates glucose transport via enhancing insulin signaling transduction in the absence of insulin and raise the possibility that gallic acid can be an insulin-mimetic agent.
\nThe effect of gallic acid (GA) on phosphorylation status of Akt Ser473 and AMPKα Thr172 in skeletal muscle. Isolated epitrochlearis muscles were incubated in the absence (Basal) or presence of epigallocatechin gallate (EGCG) (2.2 μM), caffeine (150 μM), Pu-erh tea hot-water extract (PTE) (1.5 mg/mL), GA (820 μM), or insulin (1 μM) for 30 min. The concentrations of GA, caffeine, and EGCG were adjusted to the concentration of each constituent to the level corresponding to 1.5 mg/mL of PTE. Muscle lysates were then analyzed for phosphorylation of Akt Ser473 (pAkt) and AMPKα Thr172 (pAMPK) by western blot analysis. Representative immunoblots are shown. This figure was adapted from Ma et al. with permission by the publisher.
Salicylic acid (salicylate or 2-hydroxybenzoic acid) is one of the oldest drugs in clinical practice. Salicylate has been used for treating pain, fever, and inflammation, but recent evidences have accumulated the effectiveness of treating T2DM. Over 100 years ago, Ebstein [85] and Williamson [86] showed that high doses of sodium salicylate (5–7.5 g/day) reduced glucosuria in diabetic patients. After that, additional trials have been reported similar effects that the treatment of sodium salicylate improved glucose homeostasis [87–94]. A recent meta-analysis of salicylates, including sodium salicylate, aspirin (acetylsalicylate), and salsalate (2-[2-hydroxybenzoyl]oxybenzoic acid), for T2DM showed that any doses of salicylates reduce glycated hemoglobin (HbA1c) level and that high doses of sodium salicylate (>3000 mg/day) improve fasting plasma glucose level [95].
\nThe mechanism of antidiabetic action of salicylate might be attributed to the stimulation of both insulin-dependent and insulin-independent glucose transport. Kim et al. [96] demonstrated that infusion of lipid into tail vain of rats for 5 h impaired insulin-dependent glucose transport in skeletal muscle, whereas the impairment was attenuated by concomitant infusion of sodium salicylate (7 mg/kg/h). In that situation, the decreases in insulin-dependent glucose transport in skeletal muscle were associated with the reduction of tyrosine phosphorylation of IRS-1 and PI3K activity [96]. Salicylate is a known inhibitor of IKK/NF-κB signaling. Kim et al. [96] also revealed that the defects of insulin-dependent glucose transport with lipid infusion were not induced in IKK-β knockout mice. Overall, these results indicate that salicylate may protect the defects of fat-induced insulin resistance in skeletal muscle by preserving insulin signaling transduction via the inhibition of IKK/NF-κB signaling.
\nRecent work by us first showed that the treatment of sodium salicylate (5 mM, 30 min) stimulated insulin-independent glucose transport in rat-isolated skeletal muscles [97]. The stimulation of insulin-independent glucose transport by sodium salicylate may be explained by the activation of AMPK. A study found that sodium salicylate (>1 mM) activates AMPK in human embryonic kidney cells directly by binding to AMPK (1–10 mM) and indirectly by energy depletion (>10 mM) [98]. In addition, we showed that incubation of isolated rat skeletal muscles with sodium salicylate (>5 mM) increased AMPKα Thr172 phosphorylation and AMPK activity accompanied by the reduction of energy status (ATP, PCr, and glycogen) [97]. The depletion of energy levels in response to sodium salicylate stimulation was also observed in Drosophila tissue culture (SL2) cells [99] and neutrophils [100]. Inhibition of oxidative phosphorylation by sodium salicylate was suggested to cause to energy depletion [101]. These findings suggest that salicylate stimulates AMPK via both energy-dependent and energy-independent processes in skeletal muscle. It seems that CaMKK signaling is not involved in salicylate-induced AMPK activation because the CaMKK inhibitor STO-609 had no effect on responses to salicylate [98].
\n\n
Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is derived from the biosynthesis of caffeic acid and has antidiabetic effects. Chronic treatment with ferulic acid showed a hypoglycemic effect in diabetic mice [106–108]. A study reported that ferulic acid stimulated insulin-independent glucose transport in L6 skeletal muscle cells in a dose-dependent (<50 μM) and time-dependent (<5 h) manners [63]. In contrast, another study showed that treatment with ferulic acid (250–500 μM) inhibited insulin-independent glucose transport in L6 skeletal muscle cells [109]. Therefore, further studies are needed to clear the effect of ferulic acid on glucose transport system.
\nSinapic acid (sinapinic acid or 4-hydroxy-3,5-dimethoxycinnamic acid) is known to have an anti-inflammatory action through NF-κB inactivation [110]. Inflammation links with the progress of T2DM, and thus, it is indicated the merit of sinapic acid in the treatment of T2DM. Indeed, a single administration of sinapic acid (10–30 mg/kg) dose-dependently reduced the hyperglycemia of STZ-induced diabetic rats [111, 112]. Further, sinapic acid (0.1–10 μM) stimulated enhanced insulin-independent glucose transport in isolated rat skeletal muscle and L6 skeletal muscle cells [112]. Repeated treatment with sinapic acid (25 mg/kg) for 3 days increased the gene expression of GLUT4 in skeletal muscle of STZ-induced diabetic rats [112]. Considering that AMPK promotes GLUT4 expression [66–68], sinapic acid-induced stimulation of glucose transport and GLUT4 expression may be mediated by AMPK activation.
\nPhytomedicine is becoming to be an important medical treatment, and thus it is necessary to understand the molecular mechanism underlying the effectiveness of phytochemicals on health promotion. In this chapter, we reviewed the relationship between phenolic acids and T2DM focusing on skeletal muscle glucose transport systems. Among many phenolic acids, it has been reported that caffeic acid, chlorogenic acid, gallic acid, salicylic acid,
Physical exercise is a powerful tool that promotes good health, and it reduces the risk of T2DM. Skeletal muscle AMPK is considered to be a candidate therapeutic target molecule in T2DM since AMPK is activated by physical exercise. If skeletal muscle AMPK could be activated by alternative approaches including phytochemicals, it would benefit people who are unable to engage in physical exercise. As described above, caffeic acid has no capacity for enhancing contraction-induced AMPK activity. This finding suggests that caffeic acid may not strengthen the exercise benefit but simultaneously means that caffeic acid and contraction have a common mechanism to stimulating insulin-independent glucose transport through AMPK. Therefore, caffeic acid has a potential as an exercise-mimetic stimulator for glucose transport systems. Thus, we expect that some kinds of phytochemicals have potential to act as preventive and therapeutic agents for T2DM.
\nPhenolic acids | \nInsulin-dependent glucose transport | \nInsulin-independent glucose transport | \nMolecular responses | \n
---|---|---|---|
Caffeic acid | \n↑ (insulin resistance state) | \n↑ | \nAMPK activity ↑, Energy status ↓, NF-κB activity ↓ | \n
Chlorogenic acid | \n— | \n↑ | \nAMPK activity ↑ (>1 mM, >60 min) AMPK expression ↑, CaMKK expression ↑ | \n
Gallic acid | \n— | \n↑ | \nAkt activity ↑, AMPK activity → | \n
Salicylic acid | \n↑ (lipid infused state) | \n↑ | \nInsulin-stimulated IRS-1 tyrosine phosphorylation ↑, Insulin-stimulated PI3K activity ↑ NF-κB activity ↓, AMPK activity ↑ Energy status ↓, CaMKK activity → | \n
— | \n↑ | \nAMPK activity ↑ | \n|
Ferulic acid | \n— | \n↑ | \n— | \n
Synapic acid | \n— | \n↑ | \nGLUT4 gene expression ↑ | \n
Summary of the effect of phenolic acids on skeletal muscle glucose transport.
AMPK, 5′AMP-activated protein kinase; CaMKK, Ca2+/calmodulin-dependent protein kinase kinase; GLUT4, glucose transporter 4; IRS-1, insulin receptor substrate 1; NF-κB, nuclear factor-κB; PI3K, phosphatydilinositol-3 kinase; ↑, increase; ↓, decrease; →, no change; —, no study.
This work was supported, in part, by JSPS KAKENHI Grant Numbers 26560371 (TE), 16K13022 (KG), 26350818 (KG), and 15K01711 (TH); JSPS Fellows (ST, 13J00300); the Ministry of Agriculture, Forestry and Fisheries; the Integration Research for Agriculture and Interdisciplinary Fields (funding agency, Bio-oriented Technology Research Advancement Institution, NARO) (TH, 14532022); the Council for Science, Technology and Innovation; SIP (funding agency, NARO) (TH, 14533567); and research grants from the Nakatomi Foundation (TE), the All Japan Coffee Association (TE and KG), the Vascular Disease Research Foundation (TH), the Naito Foundation (KG), the Descente Sports Foundation (KG), and the Graduate School of Health Sciences, Toyohashi Sozo University (KG).
\nThe impact of Haber-Bosch process on modern agriculture may not be overemphasized. It led to the invention of inorganic fertilizers that powered global green revolution, minimized food scarcity, and improved human and animal nutrition. In his noble lecture, Fritz Haber (The 1918 noble laureate for chemistry; for the Haber-Bosch process) alluded that his impetuses for creation of ammonia from the elements were to meet increasing human food requirements, and replenish soil nitrogen extracted by harvested crops when he concluded: “
Ammonia (NH3) air pollution from animal husbandry, fertilizer production and application has also been documented and reported [12, 13, 14]. About 94% of NH3 emissions in Italy emanate from agricultural operations [15], and in 2013 and 2018, agriculture contributed 93% of all ammonia emissions in the European Union [16, 17]. In the United States, agricultural runoff and drainage accounts for 89% of the total nitrogen inputs into the Mississippi River [18], contributing to hypoxic zone of the Gulf of Mexico [19]. In France, about 89% of residual nitrogen contamination of water resources and marine environments is attributed to mineral fertilizer and animal manure [8]. Similarly, nitrate contamination of surface and ground water is associated with agricultural use of fertilizers and manures [7, 8, 20, 21, 22, 23]. Nitrous oxide (N2O) is a greenhouse gas that contributes to stratospheric ozone shield depletion and climate change [10]. Nitrogen fertilizer and manure contribute 92% of all N2O attributable to agriculture in the USA [24, 25]. In Italy and China, fertilizer accounts for about 68% of annual N2O emissions [15, 26]. Chemical fertilizer and manure are major contributors to external costs such as eutrophication and acidification of ecosystems [21, 27, 28, 29, 30]. Annually, up to € 320 (US$ 372.495) billion damage is associated with the use of nitrogen fertilizers in the European Union compared to direct economic benefit to farmers, in terms of crops grown, estimated at up to € 80 (US$ 93.124) billion [31]. Report currency, € 1.0 ≈ US$ 1.164 based on currency converter site: https://www1.oanda.com/currency/converter/as at Friday 22nd October 2021. Furthermore, inorganic fertilizers are not cheap, and may be used in large quantities. As at the second week of September 2021, the cost of 1 kg of nutrient fertilizer could range from ≈ US$ 0.375 for liquid nitrogen (as urea) to US$ 0.807 for dry phosphorus (as P2O5) [Ramsdell F&M Ltd. Brookings, SD USA]. In 2019, approximately 188.54 x 109 kg nutrient fertilizers (including 107.74 x 109 kg N, 43.41 x 109 kg P2O5, and 37.39 x 109 kg K2O) were consumed in agricultural production globally [32].
Due to outlined adverse effects and financial exigencies of chemical fertilizers, a more sustainable, environmentally benign, and cost-effective fertilizer system is desired. Digestate in the context of circular economy could play a prominent role. In this chapter, cost implications of using liquid fraction (LF) of cassava peeling residue (CPR) digestate, to supplement chemical fertilizers required for cassava root production are analyzed and presented (Figure 1).
Graphical representation of the objectives and summary of this chapter.
Circular economy is a credible intervention tool to minimize GHG emissions, limit global warming and ecosystem degradation. The circular economic model maximizes material and product conservation; prudent consumption; eco-friendly biorefinery; recyclability and reusability; green- smart mobility and renewable energy; systems thinking, innovative business models and policies; wasteless design and zero waste cities, as well as generation of useful products out of waste [33, 34, 35, 36, 37, 38, 39, 40]. Anaerobic digestion (AD) is a responsive technology that could rise to the occasion. In the context of biorefinery platform, sustainability, and circular economy, AD transforms organic matter to two major coproducts: biogas fuel and digestate [41]. Digestate has soil amendment and biofertilizer potentials.
Digestate enhances soil biological stability and enzymatic activities [42]; enriches microbial biomass [42, 43]; abates nutrients leaching and remediates metal contaminants [43, 44, 45]; conditions the soil and boosts plant nutrients, stimulates growth of beneficial microbes, improves buffering capacity, and physical properties such as texture, aeration, bulk density, hydraulic conductivity, and moisture retention capacity [46, 47, 48, 49]. In comparison to chemical fertilizers, digestate biofertilizers offer better ecosystem services, values, and life cycle assessment accounting [50]; including lower energy consumption [51, 52, 53], lower ammonia air pollution [15], lower GHG emissions [53, 54, 55], better soil carbon sequestration [54, 56], reduced soil erosion [54, 57, 58], and increased biodiversity [59].
To exploit these benefits and advantages, various organic substrates have been used for digestate creation via the AD process. At least 120 items have been identified in published scientific literature [41], but CPR is not one of them. Indeed, there is scarcity of information on nutrient content, speciation, agronomic properties and values of LF of digestates from AD of single feedstocks in general [60]; and LF of digestate derived from AD of CPR as single feedstock in particular [41, 61].
The only information on primary macronutrients (i.e., nitrogen (N), phosphorus (P), and potassium (K)) content of LF digestate of CPR as sole feedstock found in literature is presented in Table 1. For perspective, the values are compared with LF of digestates derived from other feedstocks in Tables 2–4 respectively for N, P, and K. The values for each Table are presented in descending magnitude order. It can be seen that LF of CPR digestate is high in N and K, but low in P. Apart from livestock manure, most LF digestates with higher nutrient values are derived from AD of multiple feedstocks (Tables 2–4). Co-digestion of feedstocks may benefit from coactive effects.
S/N | Nutrient | Value [mg/L] |
---|---|---|
1 | Total Kjeldahl nitrogen (N) | 573 |
2 | Total phosphorus (P) | 31 |
3 | Total Potassium (K) | 1066 |
Macronutrients (N, P, K) content of liquid fraction of CPR digestate [41].
S/N | Feedstock | N Value [mg/L] | Reference |
---|---|---|---|
1 | Cow manure & slurry (70%), maize silage (20%) and grass silage (10%) | 5591 | [62] |
2 | Dairy manure | 4723 | [63] |
3 | Cattle & pig slurries (main feedstocks), various food wastes (co-substrates) | 4268–4507 | [64] |
4 | Dairy cow slurry | 2800–4500 | [65] |
5 | Organic waste (Kitchen garbage, spoilt food, etc.) | 3610–4120 | [66] |
6 | Energy crops e.g., silage maize (92%) and pig slurry (8%) | 4035 | [67] |
7 | Animal manure and energy crops | 4000 | [68] |
8 | Biowaste | 2457–3950 | [69] |
9 | Sewage sludge | 2700–3800 | [70] |
10 | Sewage sludge + Acid cheese whey | 2800–3750 | [70] |
11 | Dairy manure | 3007 | [71] |
12 | Biowaste and kitchen refuse | 1010–2780 | [72] |
13 | Municipal wastewater | 2667 | [73] |
14 | Maize silage and distillery stillage | 2620 | [74] |
15 | Poultry litter | 1570–2473 | [75] |
16 | Bio-slurry | 170–2240 | [76] |
17 | Source separated household waste | 2200 | [77] |
18 | Municipal solid waste | 1308–1569 | [78] |
19 | Swine manure | 1135 | [79] |
20 | Waste activated sludge and organic fraction of municipal solid waste | 425–850 | [80] |
21 | Sewage sludge (half-synthetic) | 820 | [81] |
22 | Piggery farm effluent | 774 | [82] |
23 | Yeast production wastewater | 703 | [83] |
24 | Cattle slurry and glycerin | 600 | [84] |
25 | Municipal wastewater sludge | 280–590 | [85] |
27 | Sewage sludge and organic fraction of municipal solid waste | 355–535 | [86] |
28 | Municipal wastewater | 435–520 | [87] |
29 | Swine wastewater | 460 | [88] |
30 | Starch processing wastewater | 240–383 | [89] |
31 | Starch processing wastewater | 265 | [90] |
32 | Piggery wastewater | 139 | [91] |
Comparison of nitrogen (N) content of liquid fraction of digestate derived from various feedstocks.
S/N | Feedstock | P Value [mg/L] | Reference |
---|---|---|---|
1 | Pig slurry | 800–1700 | [65] |
2 | Dairy cow slurry | 200–1000 | [65] |
3 | Dairy manure | 802 | [63] |
4 | Sewage sludge | 590–680 | [70] |
5 | Sewage sludge + Acid cheese whey | 500–550 | [70] |
6 | Pig manure | 492 | [92] |
7 | Energy crops (92%) and pig slurry (8%) | 412 | [67] |
8 | Municipal wastewater | 381 | [73] |
9 | Bio-slurry | 56–320 | [76] |
10 | Cattle & pig slurries (main feedstocks), various food wastes (co-substrates) | 292–315 | [64] |
11 | Maize silage and distillery stillage | 270 | [74] |
12 | Fruit and vegetable food waste | 261 | [93] |
13 | Source separated household waste | 230 | [77] |
14 | Poultry litter | 154–214 | [75] |
15 | Piggery wastewater | 185 | [91] |
16 | Municipal wastewater sludge | 100–185 | [85] |
17 | Organic waste (Kitchen garbage, spoilt food, etc.) | 58–167 | [66] |
18 | Sewage sludge (half-synthetic) | 130 | [81] |
19 | Sewage sludge and organic fraction of municipal solid waste | 29–120 | [86] |
20 | Swine manure | 115 | [88] |
21 | Waste activated sludge and organic fraction of municipal solid waste | 95 | [80] |
22 | Municipal solid waste | 60–62 | [78] |
23 | Biowaste | 35–55 | [69] |
24 | Municipal wastewater | 43 | [94] |
25 | Starch processing wastewater | 23–40 | [89] |
27 | Starch processing wastewater | 28 | [90] |
28 | Swine manure | 25 | [79] |
29 | Algal biomass ( | 7 | [95] |
30 | Yeast production wastewater | 7 | [83] |
Comparison of phosphorus (P) content of liquid fraction of digestate derived from various feedstocks.
S/N | Feedstock | K Value [mg/L] | Reference |
---|---|---|---|
1 | Animal manure and energy crops | 3500 | [68] |
2 | Pig manure | 3258 | [92] |
3 | Cattle & pig slurries (main feedstocks), various food wastes (co-substrates) | 1337–2850 | [64] |
4 | Organic fraction of municipal solid waste | 700–2216 | [96] |
5 | Poultry litter | 1632–2100 | [75] |
6 | Cattle slurry and 10% orange peel residue | 1200 | [84] |
7 | Source separated household waste | 1130 | [77] |
8 | Cattle slurry and 5% orange peel residue | 1100 | [84] |
[ | |||
10 | Baker’s yeast industry wastewater | 827 | [97] |
11 | Swine manure | 809 | [79] |
12 | Cattle slurry and glycerin | 800 | [84] |
13 | Bio-slurry | 100–434 | [76] |
14 | Starch processing wastewater | 102–176 | [89] |
15 | Starch processing wastewater | 174 | [90] |
16 | Sewage sludge and organic fraction of municipal solid waste | 28–33 | [86] |
17 | Waste activated sludge and organic fraction of municipal solid waste | 30 | [80] |
Comparison of potassium (K) content of liquid fraction of digestate derived from various feedstocks.
The nutrient values presented in Table 1 are for digestate derived from 800 g CPR accumulated in the 3 L working volume of AD reactor [41, 61]. Therefore, total nutrient credits for the 800 g CPR are:
N = 573 mg/L × 3 L = 1719 mg (1.719 g).
P = 31 mg/L × 3 L = 93 mg (0.093 g).
K = 1066 mg/L × 3 L = 3198 mg (3.198 g).
With the nutrients credit for 800 g (0.8 kg) CPR established, estimation of corresponding nutrient credit for CPR generated from 1000 kg cassava root becomes possible. It has been reported that CPR constitutes about 19% mass fraction of fresh cassava root [98]. Consequently, 1000 kg cassava root would yield 190 kg CPR. Hence, N, P, and K fertilizer credits for CPR generated from 1000 kg cassava root are estimated as:
N = 190 kg/0.8 kg × 1.719 g.
P = 190 kg/0.8 kg × 0.093 g.
K = 190 kg/0.8 kg × 3.198 g.
The results are presented in Table 5
Nutrient | Quantity in LF of CPR digestate from 1000 kg cassava root | |
---|---|---|
[g] | [kg] | |
Nitrogen (N) | 408.2625 | 0.4082625 |
Phosphorus (P) | 22.0875 | 0.0220875 |
Potassium (K) | 759.525 | 0.759525 |
Nutrient credit for LF of digestate of CPR derived from 1000 kg cassava root.
Cassava crop is forbearing of harsh growing conditions such as drought, acidic soil, marginal land, varied elevation, swings of temperature and rainfall [99, 100]. However, research has shown that cassava is also responsive to adequate soil fertility and fertilizer application [101, 102, 103]. The equivalent root productivities in response to three cases of chemical fertilizer input are presented in Table 6.
Case | Fertilizer Input [kg/ha] | Root Output [kg/ha] | ||
---|---|---|---|---|
Nitrogen (N) | Phosphorus (P2O5) | Potassium (K2O) | ||
A | 1.78 | 0.44 | 2.28 | 1000 |
B | 1.81 | 1.03 | 3.30 | 1000 |
C | 1.38 | 0.51 | 4.38 | 1000 |
Nutrient requirements for cassava root production (Derived from ref. [102]).
From the atomic weights of P, K and O, the elemental nutrient equivalent of the oxide forms (P2O5 and K2O) could be computed with the equations:
Consequently, the total P and total K corresponding to the total N required for the three cases of cassava root production outlined in Table 6 are estimated and presented in Table 7.
Case | Fertilizer Input [kg/ha] | Root Output [kg/ha] | ||
---|---|---|---|---|
Nitrogen (N) | Phosphorus (P) | Potassium (K) | ||
A | 1.78 | 0.19228 | 1.8924 | 1000 |
B | 1.81 | 0.45011 | 2.739 | 1000 |
C | 1.38 | 0.22287 | 3.6354 | 1000 |
Mean | 1.6567 | 0.2884 | 2.7556 | 1000 |
Elemental nutrient requirements for cassava root production (Derived from Table 6).
Based on nutrients required to produce one metric ton (1000 kg) of cassava root shown in Table 7, and the nutrient credit for LF of digestate of CPR generated from 1000 kg cassava root presented in Table 5, the capability of LF of CPR digestate to supplant chemical fertilizer in cassava root production is estimated and outlined in Table 8. The proportion of production nutrient substituted range from about 23–30% for nitrogen; 5–11% for phosphorus; and 21–40% for potassium.
Case | Nutrient | Nutrient required for production of 1000 kg cassava root (From: Table 7) [kg] | Nutrient credit for liquid fraction (LF) of digestate of CPR generated from 1000 kg cassava root (From: Table 5) [kg] | Proportion of nutrient required for production of 1000 kg cassava root supplanted by LF of digestate of CPR generated from 1000 kg cassava root [%] |
---|---|---|---|---|
A | Nitrogen (N) | 1.78 | 0.408 | 22.92 |
Phosphorus (P) | 0.192 | 0.022 | 11.46 | |
Potassium (K) | 1.892 | 0.760 | 40.17 | |
B | Nitrogen (N) | 1.81 | 0.408 | 22.54 |
Phosphorus (P) | 0.450 | 0.022 | 4.89 | |
Potassium (K) | 2.739 | 0.760 | 27.75 | |
C | Nitrogen (N) | 1.38 | 0.408 | 29.56 |
Phosphorus (P) | 0.223 | 0.022 | 9.87 | |
Potassium (K) | 3.635 | 0.760 | 20.91 | |
Mean | Nitrogen (N) | 1.6567 | 0.408 | 24.63 |
Phosphorus (P) | 0.2884 | 0.022 | 7.63 | |
Potassium (K) | 2.7556 | 0.760 | 27.58 |
From the mean nutrient values in Table 8, about 25, 8, and 28% of N, P, and K respectively required for production of 1000 kg cassava root, and sourced from inorganic fertilizers are supplanted by liquid fraction of CPR digestate. The cost implications are analyzed and presented in Table 9. The analyses indicate that about 25% of the total financial cost of inorganic fertilizers is supplanted by liquid fraction of CPR digestate (Table 9).
Variable | Unit | Nutrient | Total | ||
---|---|---|---|---|---|
Nitrogen (N) | Phosphorus (P) | Potassium (K) | |||
Unit cost of nutrient* | US$/kg | 1.34 | 3.95 | 2.33 | — |
Nutrient required for production of 1000 kg cassava root | kg | 1.6567 | 0.2884 | 2.7556 | — |
Cost of nutrient required for production of 1000 kg cassava root | US$ | 2.22 | 1.1392 | 6.4205 | 9.7797 |
Nutrient from liquid fraction of digestate of CPR generated from 1000 kg cassava root | kg | 0.408 | 0.022 | 0.760 | — |
Cost credit of nutrient from liquid fraction of digestate of CPR generated from 1000 kg cassava root | US$ | 0.5467 | 0.0869 | 1.7708 | 2.4044 |
Proportion of cost of nutrient required for production of 1000 kg cassava root saved by liquid fraction of CPR digestate | % | 24.63 | 7.63 | 27.58 | 24.59 |
Cost implications of supplanting chemical fertilizers with liquid fraction of CPR digestate in cassava root production.
Unit cost of liquid fertilizer derived from price data supplied by Ramsdell F&M Ltd. Brookings, SD USA. (Price as at 13th September 2021).
In 2019, a total of 96 recorded countries/territories produced about 303.569 x 109 kg cassava root globally. The output ranged from 5000 kg for Maldives to 59.194 × 109 kg for Nigeria [104]. At 19% CPR mass fraction composition, 57.678 × 109 kg of CPR would be generated from the global root output. This quantity of CPR could be transformed to biogas and digestate via AD. Whole digestate could be separated into liquid and solid fractions using appropriate technologies [41]. The liquid fraction of CPR digestate could then be utilized to supplant inorganic fertilizers required for cassava root production. The cost data generated and presented in Table 9 are applied to estimate the pecuniary value of global fertilizer savings from liquid fraction of CPR digestate substitution of chemical fertilizers. The results for each of the 96 countries/territories that produced cassava root in 2019 are presented in Table 10. Total global cost savings is about US$ 141.019 (€ 121.130) million. The range is from US$ 2.323 (€ 1.995) for Maldives, to US$ 27.498 (€ 23.620) million for Nigeria.
S/N | Country | 2019 Cassava root output [x 109 kg]a | CPR generated from 2019 root output @ 19% CPR mass fraction [x 109 kg] | Cost of chemical fertilizer required for 2019 root output [x 106 US$] | Potential savings from liquid fraction digestate derived from 2019 CPR output. (≈ 25% total fertilizer cost) [× 106 US$] |
---|---|---|---|---|---|
1 | Nigeria | 59.193708 | 11.24680452 | 109.9903742 | 27.49759354 |
2 | Democratic Republic of the Congo | 40.050112 | 7.60952128 | 74.41883526 | 18.60470882 |
3 | Thailand | 31.079966 | 5.90519354 | 57.75102126 | 14.43775532 |
4 | Ghana | 22.447635 | 4.26505065 | 41.71091584 | 10.42772896 |
5 | Brazil | 17.497115 | 3.32445185 | 32.51214176 | 8.128035439 |
6 | Indonesia | 14.586693 | 2.77147167 | 27.10416149 | 6.776040373 |
7 | Cambodia | 13.737921 | 2.61020499 | 25.52702174 | 6.381755435 |
8 | Viet Nam | 10.105224 | 1.91999256 | 18.77695124 | 4.69423781 |
9 | Angola | 9.000432 | 1.71008208 | 16.72408972 | 4.181022429 |
10 | United Republic of Tanzania | 8.184093 | 1.55497767 | 15.20721512 | 3.80180378 |
11 | Cameroon | 6.092549 | 1.15758431 | 11.32082728 | 2.830206819 |
12 | Malawi | 5.667887 | 1.07689853 | 10.53174455 | 2.632936138 |
13 | Côte d’Ivoire | 5.238244 | 0.99526636 | 9.733406421 | 2.433351605 |
14 | China | 4.986557 | 0.94744583 | 9.265735984 | 2.316433996 |
15 | India | 4.976 | 0.94544 | 9.246119568 | 2.311529892 |
16 | China, mainland | 4.975472 | 0.94533968 | 9.245138468 | 2.311284617 |
17 | Sierra Leone | 4.588612 | 0.87183628 | 8.526297268 | 2.131574317 |
18 | Zambia | 4.036584 | 0.76695096 | 7.500550304 | 1.875137576 |
19 | Mozambique | 3.987446 | 0.75761474 | 7.409244873 | 1.852311218 |
20 | Benin | 3.894777 | 0.74000763 | 7.237052619 | 1.809263155 |
21 | Paraguay | 3.384 | 0.64296 | 6.287955912 | 1.571988978 |
22 | Madagascar | 2.913862 | 0.55363378 | 5.414372278 | 1.35359307 |
23 | Uganda | 2.841625 | 0.53990875 | 5.280145602 | 1.320036401 |
24 | Philippines | 2.6308 | 0.499852 | 4.888402604 | 1.222100651 |
25 | Burundi | 2.408958 | 0.45770202 | 4.476188445 | 1.119047111 |
26 | Lao People’s Democratic Republic | 2.258702 | 0.42915338 | 4.19699131 | 1.049247828 |
27 | Guinea | 2.145484 | 0.40764196 | 3.986616076 | 0.996654019 |
28 | Congo | 1.457028 | 0.27683532 | 2.707366379 | 0.676841595 |
29 | Peru | 1.286013 | 0.24434247 | 2.389596054 | 0.597399013 |
30 | Rwanda | 1.181825 | 0.22454675 | 2.195999851 | 0.548999963 |
31 | Togo | 1.11788 | 0.2123972 | 2.077180897 | 0.519295224 |
32 | Senegal | 1.030592 | 0.19581248 | 1.914987311 | 0.478746828 |
33 | Colombia | 1.026643 | 0.19506217 | 1.907649504 | 0.476912376 |
34 | Kenya | 0.970587 | 0.18441153 | 1.80348944 | 0.45087236 |
35 | Cuba | 0.795748 | 0.15119212 | 1.478613576 | 0.369653394 |
36 | Central African Republic | 0.730362 | 0.13876878 | 1.357117038 | 0.339279259 |
37 | South Sudan | 0.572531 | 0.10878089 | 1.06384447 | 0.265961117 |
38 | Liberia | 0.558222 | 0.10606218 | 1.037256302 | 0.259314075 |
39 | Niger | 0.513671 | 0.09759749 | 0.954474173 | 0.238618543 |
40 | Haiti | 0.507856 | 0.09649264 | 0.943669071 | 0.235917268 |
41 | Venezuela (Bolivarian Republic of) | 0.42162 | 0.0801078 | 0.783430252 | 0.195857563 |
42 | Myanmar | 0.392443 | 0.07456417 | 0.729215213 | 0.182303803 |
43 | Gabon | 0.337209 | 0.06406971 | 0.626582543 | 0.156645636 |
44 | Chad | 0.296976 | 0.05642544 | 0.551823876 | 0.137955969 |
45 | Sri Lanka | 0.281075 | 0.05340425 | 0.522277544 | 0.130569386 |
46 | Zimbabwe | 0.253835 | 0.04822865 | 0.471661728 | 0.117915432 |
47 | Nicaragua | 0.220786 | 0.04194934 | 0.41025196 | 0.10256299 |
48 | Bolivia (Plurinational State of) | 0.203327 | 0.03863213 | 0.377810642 | 0.09445266 |
49 | Argentina | 0.195852 | 0.03721188 | 0.363921023 | 0.090980256 |
50 | Dominican Republic | 0.17469 | 0.0331911 | 0.324599001 | 0.08114975 |
51 | Costa Rica | 0.159861 | 0.03037359 | 0.297044598 | 0.07426115 |
52 | Papua New Guinea | 0.155145 | 0.02947755 | 0.288281596 | 0.072070399 |
53 | Somalia | 0.093717 | 0.01780623 | 0.174139588 | 0.043534897 |
54 | Equatorial Guinea | 0.079646 | 0.01513274 | 0.147993657 | 0.036998414 |
55 | Fiji | 0.07603 | 0.0144457 | 0.141274612 | 0.035318653 |
56 | Mali | 0.070312 | 0.01335928 | 0.130649751 | 0.032662438 |
57 | Ecuador | 0.069863 | 0.01327397 | 0.129815444 | 0.032453861 |
58 | Comoros | 0.065071 | 0.01236349 | 0.120911223 | 0.030227806 |
59 | Guinea-Bissau | 0.056073 | 0.01065387 | 0.104191652 | 0.026047913 |
60 | Malaysia | 0.042267 | 0.00803073 | 0.07853813 | 0.019634533 |
61 | El Salvador | 0.029148 | 0.00553812 | 0.054161152 | 0.013540288 |
62 | Mexico | 0.027153 | 0.00515907 | 0.050454157 | 0.012613539 |
63 | Honduras | 0.026732 | 0.00507908 | 0.049671879 | 0.01241797 |
64 | Jamaica | 0.026529 | 0.00504051 | 0.049294676 | 0.012323669 |
65 | Timor-Leste | 0.021533 | 0.00409127 | 0.040011393 | 0.010002848 |
66 | Guyana | 0.01855 | 0.0035245 | 0.034468553 | 0.008617138 |
67 | Panama | 0.017234 | 0.00327446 | 0.032023236 | 0.008005809 |
68 | Gambia | 0.013174 | 0.00250306 | 0.024479176 | 0.006119794 |
69 | China, Taiwan Province of | 0.011085 | 0.00210615 | 0.020597515 | 0.005149379 |
70 | Micronesia (Federated States of) | 0.00842 | 0.0015998 | 0.015645564 | 0.003911391 |
71 | Suriname | 0.007783 | 0.00147877 | 0.014461927 | 0.003615482 |
72 | Tonga | 0.006692 | 0.00127148 | 0.012434693 | 0.003108673 |
73 | Cabo Verde | 0.005124 | 0.00097356 | 0.009521125 | 0.002380281 |
74 | Guatemala | 0.004185 | 0.00079515 | 0.007776328 | 0.001944082 |
75 | Burkina Faso | 0.004046 | 0.00076874 | 0.007518047 | 0.001879512 |
76 | French Polynesia | 0.003937 | 0.00074803 | 0.007315509 | 0.001828877 |
77 | Brunei Darussalam | 0.003382 | 0.00064258 | 0.00628424 | 0.00157106 |
78 | Solomon Islands | 0.003381 | 0.00064239 | 0.006282381 | 0.001570595 |
79 | Trinidad and Tobago | 0.002355 | 0.00044745 | 0.004375927 | 0.001093982 |
80 | Saint Lucia | 0.001459 | 0.00027721 | 0.002711031 | 0.000677758 |
81 | Sao Tome and Principe | 0.001384 | 0.00026296 | 0.00257167 | 0.000642917 |
82 | Dominica | 0.001277 | 0.00024263 | 0.002372849 | 0.000593212 |
83 | New Caledonia | 0.000832 | 0.00015808 | 0.001545975 | 0.000386494 |
84 | Belize | 0.000725 | 0.00013775 | 0.001347154 | 0.000336788 |
85 | Cook Islands | 0.000718 | 0.00013642 | 0.001334147 | 0.000333537 |
86 | Mauritius | 0.000715 | 0.00013585 | 0.001328572 | 0.000332143 |
87 | Saint Vincent and the Grenadines | 0.000586 | 0.00011134 | 0.001088872 | 0.000272218 |
88 | Barbados | 0.000486 | 0.00009234 | 0.000903057 | 0.000225764 |
89 | Samoa | 0.000474 | 0.00009006 | 0.00088076 | 0.00022019 |
90 | Seychelles | 0.000236 | 0.00004484 | 0.000438522 | 0.00010963 |
91 | Grenada | 0.000235 | 0.00004465 | 0.000436664 | 0.000109166 |
92 | Bahamas | 0.000203 | 0.00003857 | 0.000377203 | 9.43008E-05 |
93 | Puerto Rico | 0.00017 | 0.0000323 | 0.000315884 | 7.89711E-05 |
94 | Antigua and Barbuda | 0.000159 | 0.00003021 | 0.000295445 | 7.38612E-05 |
95 | Niue | 0.000044 | 0.00000836 | 8.17583E-05 | 2.04396E-05 |
96 | Maldives | 0.000005 | 0.00000095 | 9.29072E-06 | 2.32268E-06 |
97 |
Haber-Bosch process facilitated the existence of inorganic fertilizers that revolutionized crop yield, improved nutrition, and enhanced food security. However, external costs associated with the production and application of inorganic fertilizers in agriculture are prodigious. Air quality degradation, climate perturbation, eutrophication, harmful algal blooms, ocean dead zones, pollution of surface water bodies and groundwater aquifers used as potable water supply sources are notable examples. Anaerobic digestion in the context of circular economic paradigm could provide viable solution. Anaerobic digestion transforms organic wastes and residues to beneficial biogas fuel and digestate biofertilizer. This chapter analyzed and presented the cost implications of liquid fraction of cassava peeling residue (CPR) digestate to supplant chemical fertilizers required for cassava root production. About 25% of fund used to purchase the chemical fertilizers required for cassava root production could be saved with the use of liquid fraction of CPR digestate. The global pecuniary saving is estimated at US$ 0.141 (€ 0.121) billion for year 2019 cassava root output. Thus, exploitation of liquid fraction of CPR digestate would save 25% pecuniary cost of inorganic fertilizers required for cassava root production, as well as attenuate afore mentioned external costs correlated with the production and application of the inorganic fertilizers.
"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
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\\n\\nOAI-PMH
\\n\\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\\n\\nLicense
\\n\\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
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\\n\\nOA Publishing Fees
\\n\\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\\n\\nDigital Archiving Policy
\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\\n\\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\\n\\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
\\n\\n\\n"}]'},components:[{type:"htmlEditorComponent",content:'
The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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