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Relaxin treatment reverses insulin resistance in mice fed a high-fat diet.

Authors :
Bonner JS
Lantier L
Hocking KM
Kang L
Owolabi M
James FD
Bracy DP
Brophy CM
Wasserman DH
Source :
Diabetes [Diabetes] 2013 Sep; Vol. 62 (9), pp. 3251-60. Date of Electronic Publication: 2013 Jun 25.
Publication Year :
2013

Abstract

The endogenous hormone relaxin increases vascular reactivity and angiogenesis. We demonstrate that acute relaxin infusion in lean C57BL/6J mice enhances skeletal muscle perfusion and augments muscle glucose uptake during a hyperinsulinemic-euglycemic clamp. However, an acute effect was absent in mice fed a high-fat (HF) diet for 13 weeks. In contrast, mice fed an HF diet for 13 weeks and continuously treated with relaxin for the final 3 weeks of the diet exhibited decreased fasting blood glucose. Insulin-stimulated whole-body glucose disappearance and percent suppression of hepatic glucose production are corrected by chronic relaxin. The increase in peripheral glucose utilization is a result of augmented in vivo skeletal muscle glucose uptake. Relaxin intervention improves endothelial-dependent vascular reactivity and induces a two-fold proliferation in skeletal muscle capillarity. The metabolic effects of the treatment are not attributed to changes in myocellular insulin signaling. Relaxin intervention reverses the accumulation of collagen III in the liver and collagen III and collagen IV in the heart; this is induced by HF feeding. These studies show the potential of relaxin in the treatment of diet-induced insulin resistance and vascular dysfunction. Relaxin provides a novel therapeutic approach targeting the extramyocellular barriers to insulin action, which are critical to the pathogenesis of insulin resistance.

Details

Language :
English
ISSN :
1939-327X
Volume :
62
Issue :
9
Database :
MEDLINE
Journal :
Diabetes
Publication Type :
Academic Journal
Accession number :
23801576
Full Text :
https://doi.org/10.2337/db13-0033