Insulin Signaling and Heart Failure.
Authors Riehle C, Abel ED
Submitted By E. Dale Abel on 4/4/2016
Status Published
Journal Circulation research
Year 2016
Date Published 4/1/2016
Volume : Pages 118 : 1151 - 69
PubMed Reference 27034277
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