title: [Physiological basis of insulin secretion abnormalities].
abstract: The pathogenesis of type 2 diabetes is complex, with two distinct mechanisms: insulin resistance (decrease of insulin action on peripheral tissues) and insulin deficiency (impaired insulin secretion by pancreatic beta-cells). These abnormalities are due to genetic and environmental factors. Type 2 diabetes is a heterogeneous disease: besides the common form with obesity, monogenic forms (such as MODY) exist. Knowledge of these forms has permit a better understanding of the genetic factors involved in diabetes, and of their relationship with insulin resistance. In this review, we discuss the main data available on genetics of type 2 diabetes, as well as the various research approaches. Today, the genetic determinism of functional abnormalities of pancreatic beta-cell is no longer discussed. However, it is also clearly established that acquired metabolic factors may contribute to pancreatic beta-cell failure. Hyperglycaemia, even moderate, induces a reduced insulin biosynthesis potential (glucotoxicity), and the increased free fatty acid flux accelerates pancreatic beta-cell apoptosis (lipotoxicity). The role of these metabolic abnormalities in the development of type 2 diabetes is briefly described.
authors.affiliation: Service d'endocrinologie, diabète et maladies métaboliques, HUS, Université Louis-Pasteur, 67091 Strasbourg Cedex. michel.pinget@chru-strasbourgh.fr
authors.forename: M
authors.initials: M
authors.lastname: Pinget
authors.forename: S
authors.initials: S
authors.lastname: Boullu-Sanchis
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000145:classification / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008928:Mitochondria / Q000502:physiology; D012016:Reference Values
chemical_list: D007328:Insulin
vernacular_title: Les bases physiologiques des troubles de l'insulinosécrétion.