[Physiopathological fundamentals of type 2 diabetes].

Type 2 diabetes is characterized by 2 major defects: 1. a dysregulation of pancreatic hormone secretion (quantitative and qualitative (early phase, pulsatility) decrease of insulin secretion, increase in glucagon secretion); 2. a decrease in insulin action on target tissues (insulin resistance). The defects in insulin action on target tissues are characterized by a decreased in muscle glucose uptake and by an increased hepatic glucose production. These abnormalities are linked to several defects in insulin signaling mechanisms and in several steps regulating glucose metabolism (transport, key enzymes of glycogen synthesis or of mitochondrial oxidation). These postreceptors defects are amplified by the presence of high circulating concentrations of free fatty acids in obese diabetic subjects (Randle cycle). The increased hepatic glucose production is due to a stimulation of gluconeogenesis secondarily to the enhanced glucagon secretion and to the presence of high circulating concentrations of free fatty acids in obese diabetic subjects (provision of obligatory cofactors such as acetyl-CoA).