title: Beta-cell mitochondrial carriers and the diabetogenic stress response.
abstract: Mitochondria play a central role in pancreatic beta-cells by coupling metabolism of the secretagogue glucose to distal events of regulated insulin exocytosis. This process requires transports of both metabolites and nucleotides in and out of the mitochondria. The molecular identification of mitochondrial carriers and their respective contribution to beta-cell function have been uncovered only recently. In type 2 diabetes, mitochondrial dysfunction is an early event and may precipitate beta-cell loss. Under diabetogenic conditions, characterized by glucotoxicity and lipotoxicity, the expression profile of mitochondrial carriers is selectively modified. This review describes the role of mitochondrial carriers in beta-cells and the selective changes in response to glucolipotoxicity. In particular, we discuss the importance of the transfer of metabolites (pyruvate, citrate, malate, and glutamate) and nucleotides (ATP, NADH, NADPH) for beta-cell function and dysfunction. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty Diabetes Center, Geneva University Medical Centre, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Brun
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty Diabetes Center, Geneva University Medical Centre, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland. Electronic address: Pierre.Maechler@unige.ch.
authors.forename: Pierre
authors.initials: P
authors.lastname: Maechler
mesh_terms: D000818:Animals; D002952:Citric Acid Cycle; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005089:Exocytosis; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction
chemical_list: D005227:Fatty Acids; D007328:Insulin; D033681:Mitochondrial Membrane Transport Proteins; D009243:NAD; D018698:Glutamic Acid; D005947:Glucose
keywords: Beta-cell; Diabetes; Glucotoxicity; Mitochondria; Pancreatic islet