PI3K signaling: a crossroads of metabolic regulation

Insulin exerts a fundamental role in glucose metabolism. Several lines of evidence have established PI3Ks as crucial signaling crossroads of metabolic regulation. These kinases play a key role in glucose homeostasis through the generation of lipid secondary messengers upon membrane receptor activation, thus regulating liver gluconeogenesis and glycogen synthesis. While class IA Pl3Kα historically appeared as the major PI3K isoform involved in insulin-mediated glucose metabolism, emerging evidence has demonstrated the contribution of other PI3K isoforms. In this review, we focus on the prototypical insulin receptor-PI3K pathway and on the effects of its impairment on metabolism, insulin sensitivity and the molecular pathophysiology of diabetes mellitus.