[Glitazones and pancreatic function].
Type 2 diabetes is characterized by two abnormalities, insulin resistance and insulin secretion defects. Their exact mechanisms and their interrelation are still a matter of debates. Development of hyperglycaemia in type 2 diabetes requires insulin secretion abnormalities. As the principal function of pancreatic beta-cell is insulin secretion, mainly in response to a glucose stimulus, it is of utmost importance to study abnormal beta-pancreatic function during the development of type 2 diabetes. The animal model of choice for such studies is the ZDF (Zucker Diabetic Fatty) rat. Two hypothesis are commonly discussed to explain the progressive beta-cell failure during type 2 diabetes evolution: glucotoxicity, mainly related to chronic hyperglycaemia effect on secretory beta-cell function and to defective glucose utilization in skeletal muscles, and lipotoxicity, as a consequence of triglyceride accumulation in the islets of Langerhans. In fact, likely, these two phenomenons are linked together, this glucolipotoxicity leading to a cellular apoptosis, through mechanisms we describe. Thiazolidinediones (glitazones) are synthetic PPARgamma ligands. Their beneficial effect on glycaemic control in type 2 diabetic patients are well established. Several studies in ZDF rats, using rosiglitazone as a preventive diabetes treatment (early administration) or a curative one (starting administration when diabetes is well established), indicate, in this animal model, that rosiglitazone has a protective effect on pancreatic beta-cell and preserve its secretory function. These studies are described and discussed, as well as their practical implications.
Girard
J
J
INSERM U567/CNRS UMR 8104, Institut Cochin, Département d'Endocrinologie-Métabolisme, Faculté de Médecine Cochin-Port Royal, F-75674 Paris Cedex 14, France. girard@cochin.inserm.fr
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones