title: [Anatomical and functional plasticity of pancreatic beta-cells and type 2 diabetes].
abstract: The most common form of diabetes, type 2 diabetes (T2D) is a major Public Health issue which is receiving a great deal of attention both in industrial and public research, in order to develop new and more effective drugs. The hyperglycaemia of T2D is the result of two interdependent defects : decreased biological efficacy of insulin in target tissues (insulin resistance), and a decreased capacity for beta cells to secrete insulin in response to glucose. Furthermore, hyperglycaemia evolves with time and even with rigorous treatment there is a progressive deterioration of glucose homeostasis. Seventy five percent of DT2 patients are obese and show a perturbed lipid profile. beta-cell plasticity is a unique property of these cells to adapt their number and volume (beta-cell mass) and their function to the increased secretory demand linked to insulin resistance. This is well documented in physiological (pregnancy) as well in pathophysiological conditions (obesity, acromegaly). Although the lack of reliable techniques makes it very difficult to document it in humans, this property is likely altered in DT2, mainly as a consequence of the prolonged exposure of islet cells to high plasma levels of glucose and free fatty acids (gluco-lipotoxicity). The mechanisms by which hyperglycaemia and hyperlipidemia exert their deleterious effects on the beta-cell include the generation of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) and Advanced Glycosylation End Products (AGE). Altogether the prevailing clinical and experimental data urge us to consider that the pathophysiology of DT2 lies, at least in part, the inability of beta-cells to adapt their functional mass to the prevailing insulin demand. This re-evaluation of the pathophysiology of DT2 stimulates the research of new therapeutic approaches aimed at maintaining and/or restoring the functional beta-cell mass by targeting the mechanisms responsible for its decrease.
authors.affiliation: Service d'Endocrinologie et Métabolisme, Département de Médecine Interne, Centre Médical Hadassa, Université Hébraïque de Jérusalem, 91120 Jérusalem, Israël. Erol.Cerasi@huji.ac.il
authors.forename: Erol
authors.initials: E
authors.lastname: Cerasi
authors.forename: Alain
authors.initials: A
authors.lastname: Ktorza
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002455:Cell Division; D048429:Cell Size; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D006949:Hyperlipidemias / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D024821:Metabolic Syndrome / Q000503:physiopathology; D008954:Models, Biological; D009765:Obesity / Q000503:physiopathology; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species
chemical_list: D005230:Fatty Acids, Nonesterified; D017127:Glycation End Products, Advanced; D007328:Insulin; D026361:Reactive Nitrogen Species; D005947:Glucose