title: Mechanisms of beta-cell death in type 2 diabetes.
abstract: A decrease in the number of functional insulin-producing beta-cells contributes to the pathophysiology of type 2 diabetes. Opinions diverge regarding the relative contribution of a decrease in beta-cell mass versus an intrinsic defect in the secretory machinery. Here we review the evidence that glucose, dyslipidemia, cytokines, leptin, autoimmunity, and some sulfonylureas may contribute to the maladaptation of beta-cells. With respect to these causal factors, we focus on Fas, the ATP-sensitive K+ channel, insulin receptor substrate 2, oxidative stress, nuclear factor-kappaB, endoplasmic reticulum stress, and mitochondrial dysfunction as their respective mechanisms of action. Interestingly, most of these factors are involved in inflammatory processes in addition to playing a role in both the regulation of beta-cell secretory function and cell turnover. Thus, the mechanisms regulating beta-cell proliferation, apoptosis, and function are inseparable processes.
authors.affiliation: Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland. marc.donath@usz.ch
authors.forename: Marc Y
authors.initials: MY
authors.lastname: Donath
authors.forename: Jan A
authors.initials: JA
authors.lastname: Ehses
authors.forename: Kathrin
authors.initials: K
authors.lastname: Maedler
authors.forename: Desiree M
authors.initials: DM
authors.lastname: Schumann
authors.forename: Helga
authors.initials: H
authors.lastname: Ellingsgaard
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Eppler
authors.forename: Manfred
authors.initials: M
authors.lastname: Reinecke
mesh_terms: D000818:Animals; D016923:Cell Death; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000503:physiopathology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000503:physiopathology; D050417:Insulin-Secreting Cells / Q000473:pathology*; D020738:Leptin / Q000502:physiology; D012307:Risk Factors
chemical_list: D020738:Leptin