Chapters authored
Pathogenesis of Type 2 Diabetes Mellitus
Type 2 diabetes mellitus (DM2) results from the interaction between genetic and environmental factors which cause insulin resistance (IR) and deficit in insulin secretion. Genes encoding insulin-related enzymes or protein factors are candidates for the disease, most probably the insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI-3 K), calpain 10, and transcription factor 7-like 2 genes. Environmental factors that favor DM2 are android obesity, aging, glucotoxicity, and lipotoxicity. IR is the result of less insulin receptor binding, of less phosphorylation of the receptor, of IRS-1, of PI-3 K, and of glucose uptake by glucose transporters. At the hepatic level, glucose is produced by gluconeogenesis: in the muscle there is less glycogen deposition, and in adipocytes there is greater release of free fatty acids (FFA). Insulin secretion is the main pathogenic factor; relative insulin hyposecretion is not capable of compensating for the IR. Reduced incretin effect, hyperglucagonemia, and increased renal glucose reabsorption favor hyperglycemia. Disturbance of the microbiota releases proinflammatory adipocytokines which contribute to IR. Reactive oxygen species generation, caused by hyperglycemia and FFA, results in a decrease in insulin synthesis and action and also endoplasmic reticulum stress and mitochondrial dysfunction. Knowledge about the pathogenesis of DM2 has allowed the development of drugs for its treatment.
Part of the book: Type 2 Diabetes
Diabetes Mellitus: A Group of Genetic-Based Metabolic Diseases
Diabetes mellitus (DM) is a disease characterized by defects in action and/or secretion of insulin that results in chronic hyperglycemia and long-term severe vascular complications. The main clinical presentations with the proven genetic base are covered. Type 1 diabetes (DM1) is an autoimmune, heterogeneous, multifactorial, and polygenic-based disease. Selectively destroys 90% of beta cells of the pancreas, mediated by activated T lymphocytes in patients with haplotypes linked to major histocompatibility complex (MHC). Genetic and genomic studies have been carried out in family groups, demonstrating up to 15 affected chromosomal regions. Type 2 diabetes (DM2) presents genes with various polymorphisms which, together with post-genomic and environmental factors, make it more complex to understand the pathogenesis. Monogenic diabetes comprises neonatal diabetes (ND), maturity onset diabetes in young (MODY), an autosomal dominant transmission which is inherited directly in three successive generations, and the very rare mitochondrial diabetes. Latent autoimmune diabetes in adults (LADA) mainly affects patients with normal weight and initially diagnosed as DM2. Its characteristics are low levels of C-peptide in both fasting and post-glucagon tests. They present MHC alleles of susceptibility and positive autoantibodies: Anti-decarboxylase glutamic acid.
Part of the book: Cellular Metabolism and Related Disorders