title: Mitochondrial function and insulin secretion.
abstract: In the endocrine fraction of the pancreas, the β-cell rapidly reacts to fluctuations in blood glucose concentrations by adjusting the rate of insulin secretion. Glucose-sensing coupled to insulin exocytosis depends on transduction of metabolic signals into intracellular messengers recognized by the secretory machinery. Mitochondria play a central role in this process by connecting glucose metabolism to insulin release. Mitochondrial activity is primarily regulated by metabolic fluxes, but also by dynamic morphology changes and free Ca(2+) concentrations. Recent advances of mitochondrial Ca(2+) homeostasis are discussed; in particular the roles of the newly-identified mitochondrial Ca(2+) uniporter MCU and its regulatory partner MICU1, as well as the mitochondrial Na(+)-Ca(2+) exchanger. This review describes how mitochondria function both as sensors and generators of metabolic signals; such as NADPH, long chain acyl-CoA, glutamate. The coupling factors are additive to the Ca(2+) signal and participate to the amplifying pathway of glucose-stimulated insulin secretion.
authors.affiliation: Department of Cell Physiology and Metabolism, 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: D001711:Biotransformation; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; D007328:Insulin; C116241:MICU1 protein, human; C582650:MICU2 protein, human; D033681:Mitochondrial Membrane Transport Proteins; D019831:Sodium-Calcium Exchanger; D005947:Glucose; D002118:Calcium
keywords: Diabetes; Insulin secretion; Mitochondria; Pancreatic islets; β-cell