title: beta-cell stimulus - secretion coupling defects in rodent models of obesity.
abstract: Hyperinsulinemia accompanies obesity in human patients and experimental rodent models and exacerbates insulin resistance, but the causes of increased insulin secretion remain obscure. This review examines progress in defining biochemical and molecular beta-cell defects that have elucidated in the past 5 years. Some defects, such as decreased glucose transport, decreased mitochondrial FAD-linked glycerophosphate dehydrogenase activity, and altered anomeric specificity for glucose, become evident only after onset of non-insulin-dependent diabetes mellitus. Thus, these defects are unlikely to play a role in the pathogenesis of hyperinsulinemia in obesity. Other biochemical changes, including increased glucokinase and (or) hexokinase function, increased glucose cycling, and altered regulation of intracellular Ca2+ are present in obese nondiabetic animals and may therefore contribute to development of hyperinsulinemia. Few developmental studies have been performed to correlate onset of defects with environmentally and genetically mediated control mechanisms of beta-cell function. However, the availability of new molecular biology techniques should facilitate identification of factors causing hyperinsulinemia in obesity.
authors: Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada.
authors: C B
authors: CB
authors: Chan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D051381:Rats
chemical_list: D007328:Insulin; D009004:Monosaccharide Transport Proteins; D005947:Glucose