Mitochondrial signals drive insulin secretion in the pancreatic β-cell

beta-Cell nutrient sensing depends on mitochondrial function. Oxidation of nutrient-derived metabolites in the mitochondria leads to plasma membrane depolarization, Ca2+ influx and insulin granule exocytosis. Subsequent mitochondrial Ca2+ uptake further accelerates metabolism and oxidative phosphorylation. Nutrient activation also increases the mitochondrial matrix pH. This alkalinization is required to maintain elevated insulin secretion during prolonged nutrient stimulation. Together the mitochondrial Ca2+ rise and matrix alkalinization assure optimal ATP synthesis necessary for efficient activation of the triggering pathway of insulin secretion. The sustained, amplifying pathway of insulin release also depends on mitochondrial Ca2+ signals, which likely influence the generation of glucose-derived metabolites serving as coupling factors. Therefore, mitochondria are both recipients and generators of signals essential for metabolism-secretion coupling. Activation of these signaling pathways would be an attractive target for the improvement of beta-cell function and the treatment of type 2 diabetes. (C) 2011 Elsevier Ireland Ltd. All rights reserved.