title: Metabolic factors that affect beta-cell function and survival.
abstract: Several data suggest that, during the natural history of Type 2 diabetes (T2DM), whereas the degree of insulin resistance is quite stable in a single individual, insulin secretion is often progressively decreasing. The decline in beta-cell function seems, at least in part, acquired. This review focuses on data showing that chronically elevated levels of glucose and fatty acids may impair beta-cell function and, at a later stage, also affect beta-cell survival. Results obtained both in vitro and in vivo demonstrate that beta-cell function is impaired after chronic exposure to glucose and fatty acids, with many similarities between the two conditions. Basal insulin release is increased as a result of an increase of the low-Km component of glucose phosphorylation. Glucose-induced insulin release is blunted, probably due to an impairment of glucose oxidation. If the metabolic abnormality persists in vivo or the culture is prolonged in vitro, a significant increase in the rate of beta-cell death was observed, eventually leading to severe destruction of the islet architecture. An attractive hypothesis, currently under investigation, is that genetic susceptibility to diabetes may confer an increased sensitivity to the adverse effect of high glucose and non-esterified fatty acid levels on beta-cell survival.
authors.affiliation: Department of Internal Medicine, Endocrinology and Metabolism, Signorelli Diabetes Center, University of Catania, Garibaldi Hospital, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Purrello
authors.forename: A M
authors.initials: AM
authors.lastname: Rabuazzo
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051381:Rats
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin