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Groschner, LN; Alam, MR; Graier, WF.
Metabolism-secretion coupling and mitochondrial calcium activities in clonal pancreatic β-cells.
Vitam Horm. 2014; 95(3):63-86 Doi: 10.1016/B978-0-12-800174-5.00003-X
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Leading authors Med Uni Graz: Graier Wolfgang; Groschner Lukas
Co-authors Med Uni Graz: Alam Muhammad Rizwan
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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. © 2014 Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Calcium Signaling -; Clone Cells -; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Diabetes Mellitus, Type 2 - physiopathology; Energy Metabolism -; Humans -; Insulin - metabolism; Insulin Secretion -; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Mitochondria - metabolism; Models, Biological -; Pancreas - cytology; Pancreas - pathology; Pancreas - physiology; Pancreas - physiopathology; Up-Regulation -