Novel regulation of insulin secretion: the role of mitochondria.
Coupling of glucose entry to insulin secretion in pancreatic beta-cells depends on numerous intracellular metabolic steps. In this process, mitochondria play a central role, and defects in this organelle are associated with impaired glucose-evoked insulin release. In response to a glucose rise, nucleotides and metabolites are generated by mitochondria and participate, together with cytosolic Ca2+, in the stimulation of insulin exocytosis. This review describes the mitochondria-dependent pathways of regulated insulin secretion. In addition, new potential drug targets for therapeutic interventions in diabetes are discussed.
Maechler
Pierre
P
Department of Internal Medicine, University Medical Centre, rue Michel-Servet 1, CH-1211 Geneva 4, Switzerland. Pierre.Maechler@medecine.unige.ch
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D004579:Electron Transport; D005089:Exocytosis / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D009711:Nucleotides / Q000502:physiology; D015221:Potassium Channels; D011522:Protons; D019289:Pyruvic Acid / Q000378:metabolism
D004272:DNA, Mitochondrial; D007328:Insulin; D008565:Membrane Proteins; D009711:Nucleotides; D015221:Potassium Channels; D011522:Protons; C117780:mitochondrial K(ATP) channel; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D002118:Calcium