Relaxin, Insulin and Diabetes: An Intriguing Connection

Daniele      Bani; Alessandro      Pini; Samuel      Ka-Sheng Yue

Abstract

Until recently, relaxin and insulin were grouped into the same hormone superfamily because of substantial biochemical homologies. This notion has then changed with the understanding that insulin and relaxin are ligands for different receptors and signal transduction systems, namely, tyrosine kinase and G-protein-coupled receptors respectively. As a matter of fact, relaxin does not mimic the metabolic effects of insulin. The biological effects of insulin are much more clearly delineated than those of relaxin, which is traditionally viewed as a reproductive hormone involved in the maternal adjustments of pregnancy. In the last decade, evidence has been accumulating that relaxin has major effects on the heart, blood vessels and the extracellular matrix within connective tissues. In particular, pertaining to the relationships between relaxin and diabetes, relaxin was shown to promote arterial and microvascular dilation, thereby increasing organ perfusion, counteract ischemic injury, improve adverse cardiac and vascular remodeling, and promote extracellular matrix turn-over, thereby exerting anti-fibrotic effects. Thus, relaxin could blunt or delay the vascular and organ complication of diabetes. Whether relaxin may also synergize with insulin to optimize blood glucose homeostasis remains an unconfirmed issue. However, there are clues in the literature which, if gathered, speak in favor of this perspective. Moreover, preliminary data suggest that exogenous relaxin administration may improve insulin sensitivity in diabetic patients. Considering that human recombinant relaxin is under study as a novel, promising drug for the treatment of heart failure, a broader knowledge of the possible beneficial effects of relaxin in diabetes and its complications can be of interest to the scientific community.

Keywords: Diabetes, Insulin, Insulin receptor, Insulin resistance, Metabolic syndrome, Relaxin, Relaxin receptor, connective tissues, microvascular dilation, homeostasis