title: Calcium co-regulates oxidative metabolism and ATP synthase-dependent respiration in pancreatic beta cells.
abstract: Mitochondrial energy metabolism is essential for glucose-induced calcium signaling and, therefore, insulin granule exocytosis in pancreatic beta cells. Calcium signals are sensed by mitochondria acting in concert with mitochondrial substrates for the full activation of the organelle. Here we have studied glucose-induced calcium signaling and energy metabolism in INS-1E insulinoma cells and human islet beta cells. In insulin secreting cells a surprisingly large fraction of total respiration under resting conditions is ATP synthase-independent. We observe that ATP synthase-dependent respiration is markedly increased after glucose stimulation. Glucose also causes a very rapid elevation of oxidative metabolism as was followed by NAD(P)H autofluorescence. However, neither the rate of the glucose-induced increase nor the new steady-state NAD(P)H levels are significantly affected by calcium. Our findings challenge the current view, which has focused mainly on calcium-sensitive dehydrogenases as the target for the activation of mitochondrial energy metabolism. We propose a model of tight calcium-dependent regulation of oxidative metabolism and ATP synthase-dependent respiration in beta cell mitochondria. Coordinated activation of matrix dehydrogenases and respiratory chain activity by calcium allows the respiratory rate to change severalfold with only small or no alterations of the NAD(P)H/NAD(P)(+) ratio.
authors.affiliation: From the Mitochondrial Function and.
authors.forename: Umberto
authors.initials: U
authors.lastname: De Marchi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Thevenet
authors.forename: Aurelie
authors.initials: A
authors.lastname: Hermant
authors.forename: Elhadji
authors.initials: E
authors.lastname: Dioum
authors.forename: Andreas
authors.initials: A
authors.lastname: Wiederkehr
mesh_terms: D025181:ATP Synthetase Complexes / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats
chemical_list: D007328:Insulin; D009249:NADP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D025181:ATP Synthetase Complexes; D005947:Glucose; D002118:Calcium
keywords: Calcium; Energy Metabolism; Insulin; Islet; Mitochondria; NAD