Targeting mTOR Signaling in Type 2 Diabetes Mellitus and Diabetes Complications.

The mechanistic target of rapamycin (mTOR) is a pivotal regulator of cell metabolism and growth. In the form of two different multi-protein complexes, mTORC1 and mTORC2, mTOR integrates cellular energy, nutrient and hormonal signals to regulate cellular metabolic homeostasis. In type 2 diabetes mellitus (T2DM) aberrant mTOR signaling underlies its pathological conditions and end-organ complications. Substantial evidence suggests that two mTOR-mediated signaling schemes, mTORC1-p70S6 kinase 1 (S6K1) and mTORC2-protein kinase B (AKT), play a critical role in insulin sensitivity and that their dysfunction contributes to development of T2DM. This review summaries our current understanding of the role of mTOR signaling in T2DM and its associated complications, as well as the potential use of mTOR inhibitors in treatment of T2DM.