Tomohiro Suhara1,2, Yuichi Baba1,3, Briana K Shimada1, Jason K Higa1, Takashi Matsui4. 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. 2. Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan. 3. Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University, Kochi, Japan. 4. 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. tmatsui@hawaii.edu.
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. Understanding mechanisms underlying mTOR-mediated pathophysiological features in the heart is essential for developing effective therapies for cardiac diseases in the context of T2DM.
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.
Authors: Rebecca K Harston; John C McKillop; Phillip C Moschella; An Van Laer; Lakeya S Quinones; Catalin F Baicu; Sundaravadivel Balasubramanian; Michael R Zile; Dhandapani Kuppuswamy Journal: Am J Physiol Heart Circ Physiol Date: 2011-02-25 Impact factor: 4.733
Authors: Vanessa P Houde; Sophie Brûlé; William T Festuccia; Pierre-Gilles Blanchard; Kerstin Bellmann; Yves Deshaies; André Marette Journal: Diabetes Date: 2010-03-18 Impact factor: 9.461
Authors: Mirko Völkers; Haruhiro Toko; Shirin Doroudgar; Shabana Din; Pearl Quijada; Anya Y Joyo; Luis Ornelas; Eri Joyo; Donna J Thuerauf; Mathias H Konstandin; Natalie Gude; Christopher C Glembotski; Mark A Sussman Journal: Proc Natl Acad Sci U S A Date: 2013-07-10 Impact factor: 11.205
Authors: Yuichi Baba; Jason K Higa; Briana K Shimada; Kate M Horiuchi; Tomohiro Suhara; Motoi Kobayashi; Jonathan D Woo; Hiroko Aoyagi; Karra S Marh; Hiroaki Kitaoka; Takashi Matsui Journal: Am J Physiol Heart Circ Physiol Date: 2017-11-10 Impact factor: 4.733