Targeting mTOR Signaling in Type 2 Diabetes Mellitus and Diabetes Complications

Abstract

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), pathological conditions and end-organ complications can be attributed to aberrant mTOR. 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 the development of T2DM. This review summarizes 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 the treatment of T2DM.

Keywords: diabetic complications; mTOR inhibitor; mTORC1; mTORC2; pivotal regulator; type 2 diabetes mellitus.