Insulin Signaling and Heart Failure

Christian Riehle; E Dale Abel

doi:10.1161/CIRCRESAHA.116.306206

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Journal article

Open access

Peer reviewed

Insulin Signaling and Heart Failure

Christian Riehle and E Dale Abel

Circulation research, Vol.118(7), pp.1151-1169

04/01/2016

DOI: 10.1161/CIRCRESAHA.116.306206

PMCID: PMC4833475

PMID: 27034277

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Abstract

Heart failure is associated with generalized insulin resistance. Moreover, insulin-resistant states such as type 2 diabetes mellitus and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes mellitus alters the systemic and neurohumoral milieu, leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead box O transcriptional signaling or glucose transport, which may also impair cardiac metabolism, structure, and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed.

Glucose Transporter Type 4 - metabolism

Insulin - physiology

Humans

Heart Failure - physiopathology

Heart Failure - prevention & control

Heart Failure - therapy

Insulin Resistance - physiology

Myocardial Ischemia - physiopathology

Fatty Acids - metabolism

Heart Failure - etiology

Myocytes, Smooth Muscle - metabolism

Diabetes Mellitus, Type 2 - complications

Disease Models, Animal

Hyperinsulinism - physiopathology

Endothelial Cells - metabolism

Obesity - complications

Risk Factors

Obesity - physiopathology

Receptor, Insulin - physiology

Ventricular Remodeling - physiology

Forecasting

Disease Progression

Protein Transport

Animals

Diabetes Mellitus, Type 2 - physiopathology

Mitochondria, Heart - physiology

Myocardial Ischemia - complications

Glucose - metabolism

Myocytes, Cardiac - metabolism

Signal Transduction - physiology

Dietary Fats - toxicity

Details

Title: Subtitle: Insulin Signaling and Heart Failure
Creators: Christian Riehle - From the Division of Endocrinology and Metabolism, Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City
E Dale Abel - From the Division of Endocrinology and Metabolism, Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City. DRCadmin@uiowa.edu
Resource Type: Journal article
Publication Details: Circulation research, Vol.118(7), pp.1151-1169
Publisher: United States
DOI: 10.1161/CIRCRESAHA.116.306206
PMID: 27034277
PMCID: PMC4833475
ISSN: 0009-7330
eISSN: 1524-4571
Grant note: R01 HL73167 / NHLBI NIH HHS R01 HL070070 / NHLBI NIH HHS R01 HL108379 / NHLBI NIH HHS R01 DK092065 / NIDDK NIH HHS U01 HL087947 / NHLBI NIH HHS R21 DK073590 / NIDDK NIH HHS R01HL10837 / NHLBI NIH HHS R01 HL112413 / NHLBI NIH HHS R01 HL12357 / NHLBI NIH HHS R01DK092065 / NIDDK NIH HHS R01 HL073167 / NHLBI NIH HHS R21DK073590 / NIDDK NIH HHS R01 HL127764 / NHLBI NIH HHS
Language: English
Date published: 04/01/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025263602771

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