title: Insulin Signaling and Heart Failure.
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.
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Riehle
authors.affiliation: 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.
authors.forename: E Dale
authors.initials: ED
authors.lastname: Abel
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology; D004041:Dietary Fats / Q000633:toxicity; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005544:Forecasting; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology; D008929:Mitochondria, Heart / Q000502:physiology; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000503:physiopathology; D021381:Protein Transport; D011972:Receptor, Insulin / Q000502:physiology; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D007328:Insulin; D011972:Receptor, Insulin; D005947:Glucose
keywords: diabetes mellitus; heart failure; insulin receptor; insulin resistance; myocardium