In beta-cells, mitochondria integrate and generate metabolic signals controlling insulin secretion.
Pancreatic beta-cells are unique neuroendocrine cells displaying the peculiar feature of responding to nutrients, principally glucose, as primary stimulus. This requires translation of a metabolic substrate into intracellular messengers recognized by the exocytotic machinery. Central to this signal transduction mechanism, mitochondria integrate and generate metabolic signals, thereby coupling glucose recognition to insulin secretion. In response to a glucose rise, nucleotides and metabolites are generated by mitochondria and participate, together with cytosolic calcium, to the stimulation of insulin exocytosis. This review describes the mitochondrion-dependent pathways of regulated insulin secretion. In particular, importance of cataplerotic and anaplerotic processes is discussed, with special attention to the mitochondrial enzyme glutamate dehydrogenase. Mitochondrial defects, such as mutations and reactive oxygen species production, are presented in the context of beta-cell failure in the course of type 2 diabetes.
Maechler
Pierre
P
Department of Cell Physiology and Metabolism, University Medical Centre, Geneva, Switzerland. Pierre.Maechler@medecine.unige.ch
Carobbio
Stefania
S
Rubi
Blanca
B
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology* / Q000648:ultrastructure; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D045222:Electron Transport Chain Complex Proteins; D007328:Insulin; D009243:NAD; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005969:Glutamate Dehydrogenase