Relaxin Treatment Reverses Insulin Resistance in High Fat-Fed Mice

  1. David H. Wasserman1,2
  1. 1Department of Molecular Physiology and Biophysics,
  2. 2Mouse Metabolic Phenotyping Center,
  3. 3Department of Surgery Division of Vascular Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
  1. Corresponding author: Jeffrey S. Bonner jeffrey.s.bonner{at}vanderbilt.edu

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, acute effect was absent in mice fed a high fat (HF) diet for 13 weeks. In contrast, mice fed a HF diet for 13 weeks and continuously treated with relaxin for the final 3 weeks of the diet exhibit decreased fasting 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 2-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 -IV in the heart induced by high fat-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.

  • Received January 8, 2013.
  • Accepted May 23, 2013.

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