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

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

Research output: Contribution to journalReview article

14 Citations (Scopus)

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.

Original languageEnglish
Article number38
JournalCurrent Diabetes Reports
Volume17
Issue number6
DOIs
Publication statusPublished - 2017 Jun 1

Fingerprint

Sirolimus
Type 2 Diabetes Mellitus
Heart Diseases
Insulin Receptor Substrate Proteins
Cardiomegaly
Cardiac Myocytes
Heart Failure
Myocardial Infarction
Insulin

Keywords

  • Cardiovascular disease
  • Cell signaling
  • Diabetes mellitus
  • Heart failure
  • mTOR
  • Rapamycin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

The mTOR Signaling Pathway in Myocardial Dysfunction in Type 2 Diabetes Mellitus. / Suhara, Tomohiro; Baba, Yuichi; Shimada, Briana K.; Higa, Jason K.; Matsui, Takashi.

In: Current Diabetes Reports, Vol. 17, No. 6, 38, 01.06.2017.

Research output: Contribution to journalReview article

Suhara, Tomohiro ; Baba, Yuichi ; Shimada, Briana K. ; Higa, Jason K. ; Matsui, Takashi. / The mTOR Signaling Pathway in Myocardial Dysfunction in Type 2 Diabetes Mellitus. In: Current Diabetes Reports. 2017 ; Vol. 17, No. 6.
@article{e176847db8bb46e68196dc8cc87c922c,
title = "The mTOR Signaling Pathway in Myocardial Dysfunction in Type 2 Diabetes Mellitus",
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.",
keywords = "Cardiovascular disease, Cell signaling, Diabetes mellitus, Heart failure, mTOR, Rapamycin",
author = "Tomohiro Suhara and Yuichi Baba and Shimada, {Briana K.} and Higa, {Jason K.} and Takashi Matsui",
year = "2017",
month = "6",
day = "1",
doi = "10.1007/s11892-017-0865-4",
language = "English",
volume = "17",
journal = "Current Diabetes Reports",
issn = "1534-4827",
publisher = "Current Medicine Group",
number = "6",

}

TY - JOUR

T1 - The mTOR Signaling Pathway in Myocardial Dysfunction in Type 2 Diabetes Mellitus

AU - Suhara, Tomohiro

AU - Baba, Yuichi

AU - Shimada, Briana K.

AU - Higa, Jason K.

AU - Matsui, Takashi

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

KW - Cardiovascular disease

KW - Cell signaling

KW - Diabetes mellitus

KW - Heart failure

KW - mTOR

KW - Rapamycin

UR - http://www.scopus.com/inward/record.url?scp=85018484764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018484764&partnerID=8YFLogxK

U2 - 10.1007/s11892-017-0865-4

DO - 10.1007/s11892-017-0865-4

M3 - Review article

VL - 17

JO - Current Diabetes Reports

JF - Current Diabetes Reports

SN - 1534-4827

IS - 6

M1 - 38

ER -