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

  • Pathogenesis of Type 2 Diabetes and Insulin Resistance (RM Watanabe, Section Editor)
  • Published:
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Abstract

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.

Summary

Understanding mechanisms underlying mTOR-mediated pathophysiological features in the heart is essential for developing effective therapies for cardiac diseases in the context of T2DM.

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Acknowledgements

This work was supported in part by a research grant from the Mitsukoshi Health and Welfare Foundation, Japan (TS), a research grant from Kochi Organization for Medical Reformation and Renewal, Japan (YB), and an NIH training grant (T32HL115505 to BKS).

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Authors and Affiliations

  1. Department of Anatomy, Biochemistry & Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo St., BSB no. 110, Honolulu, HI, 96813, USA

    Tomohiro Suhara, Yuichi Baba, Briana K. Shimada, Jason K. Higa & Takashi Matsui

  2. Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan

    Tomohiro Suhara

  3. Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University, Kochi, Japan

    Yuichi Baba

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  1. Tomohiro Suhara
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Correspondence to Takashi Matsui.

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Tomohiro Suhara, Yuichi Baba, Briana K. Shimada, Jason K. Higa, and Takashi Matsui declare that they have no conflict of interest.

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Since this is a review article, it does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Pathogenesis of Type 2 Diabetes and Insulin Resistance

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Suhara, T., Baba, Y., Shimada, B.K. et al. The mTOR Signaling Pathway in Myocardial Dysfunction in Type 2 Diabetes Mellitus. Curr Diab Rep 17, 38 (2017). https://doi.org/10.1007/s11892-017-0865-4

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