title: Metabolism-secretion coupling and mitochondrial calcium activities in clonal pancreatic β-cells.
abstract: Pancreatic β-cells are the only cells capable of lowering blood glucose by secreting insulin. The β-cell continuously adjusts its secretory activity to substrate availability in order to keep blood glucose levels within the physiological range--a process called metabolism-secretion coupling. Glucose is readily taken up by the β-cell and broken down into intermediates that fuel oxidative metabolism inside the mitochondria to generate ATP. The resulting increase in the ATP/ADP ratio causes closure of plasma membrane KATP channels, thereby depolarizing the cell and triggering the opening of voltage-gated Ca²⁺ channels. Consequential oscillations of cytosolic Ca²⁺ not only mediate the exocytosis of insulin granules but are also relayed to other subcellular compartments including the mitochondria, where Ca²⁺ is required to accelerate mitochondrial metabolism in response to nutrient stimulation. The mitochondrial Ca²⁺ uptake machinery plays a fundamental role in this feed-forward mechanism that guarantees sustained insulin secretion and, thus, represents a promising therapeutic target for type 2 diabetes.
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Lukas N
authors.initials: LN
authors.lastname: Groschner
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Muhammad Rizwan
authors.initials: MR
authors.lastname: Alam
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria. Electronic address: wolfgang.graier@medunigraz.at.
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Graier
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002999:Clone Cells; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004734:Energy Metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D010179:Pancreas / Q000166:cytology / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D015854:Up-Regulation
chemical_list: D007328:Insulin
keywords: Diabetes mellitus; Energy metabolism; Insulin secretion; Mitochondrial Ca(2+); β-Cell