The mTOR Signaling Pathway in Myocardial Dysfunction in Type 2 Diabetes Mellitus.

PURPOSE OF REVIEW: T2DM (type 2 diabetes mellitus) is a risk factor for heart failure. The mTOR (mechanistic target of rapamycin) is a key mediator of the insulin signaling pathway. We will discuss the role of mTOR in myocardial dysfunction in T2DM.

RECENT FINDINGS: In T2DM, chronically activated mTOR induces multiple pathological events, including a negative feedback loop that suppresses IRS (insulin receptor substrate)-1. While short-term treatment with rapamycin, an mTOR inhibitor, is a promising strategy for cardiac diseases such as acute myocardial infarction and cardiac hypertrophy in T2DM, there are many concerns about chronic usage of rapamycin. Two mTOR complexes, mTORC1 and mTORC2, affect many molecules and processes via distinct signaling pathways that regulate cardiomyocyte function and survival. Understanding mechanisms underlying mTOR-mediated pathophysiological features in the heart is essential for developing effective therapies for cardiac diseases in the context of T2DM.