Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland.
Mol Cell Endocrinol. 2012 Apr 28;353(1-2):128-37. doi: 10.1016/j.mce.2011.07.016. Epub 2011 Jul 19.
β-Cell nutrient sensing depends on mitochondrial function. Oxidation of nutrient-derived metabolites in the mitochondria leads to plasma membrane depolarization, Ca(2+) influx and insulin granule exocytosis. Subsequent mitochondrial Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 β-cell function and the treatment of type 2 diabetes.
β 细胞的营养感应依赖于线粒体功能。线粒体中营养衍生代谢物的氧化导致质膜去极化、Ca(2+)内流和胰岛素颗粒胞吐。随后的线粒体 Ca(2+)摄取进一步加速了代谢和氧化磷酸化。营养物质的激活还增加了线粒体基质的 pH 值。这种碱化作用对于维持在延长的营养刺激期间升高的胰岛素分泌是必需的。线粒体 Ca(2+)的升高和基质的碱化共同保证了最佳的 ATP 合成，这对于有效的胰岛素分泌触发途径的激活是必要的。胰岛素释放的持续放大途径也依赖于线粒体 Ca(2+)信号，这些信号可能影响作为偶联因子的葡萄糖衍生代谢物的产生。因此，线粒体既是代谢-分泌偶联所必需的信号的接收者，也是其的产生者。这些信号通路的激活将是改善β细胞功能和治疗 2 型糖尿病的有吸引力的目标。
