Mitochondrial function and insulin secretion

In the endocrine fraction of the pancreas, the β-cell rapidly reacts to fluctuations in blood glucose concentrations by adjusting the rate of insulin secretion. Glucose-sensing coupled to insulin exocytosis depends on transduction of metabolic signals into intracellular messengers recognized by the secretory machinery. Mitochondria play a central role in this process by connecting glucose metabolism to insulin release. Mitochondrial activity is primarily regulated by metabolic fluxes, but also by dynamic morphology changes and free Ca2+ concentrations. Recent advances of mitochondrial Ca2+ homeostasis are discussed; in particular the roles of the newly-identified mitochondrial Ca2+ uniporter MCU and its regulatory partner MICU1, as well as the mitochondrial Na+-Ca2+ exchanger. This review describes how mitochondria function both as sensors and generators of metabolic signals; such as NADPH, long chain acyl-CoA, glutamate. The coupling factors are additive to the Ca2+ signal and participate to the amplifying pathway of glucose-stimulated insulin secretion.