Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Angiotensin II Impairs Insulin’s Actions in Skeletal Muscle of High- but not Normal-Sodium Fed Rats (#241)

Dino Premilovac 1 , Steve Richards 1 , Michelle Keske 1 , Steve Rattigan 1
  1. Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia
Insulin increases microvascular perfusion in skeletal muscle to augment insulin-mediated glucose uptake, an effect that is lost early in the aetiology of insulin resistance. Angiotensin II (AngII) is a potent vasoconstrictor and has been implicated in the development of insulin resistance. Whether AngII inhibits insulin’s microvascular and metabolic actions in skeletal muscle to promote a state of insulin resistance remains unclear. To study this, Sprague Dawley rats received either normal (NS, 0.3% NaCl wt/wt) or high (8% NaCl wt/wt) sodium diets for four weeks. Following an overnight fast, anesthetized rats were subjected to either constant-flow perfused rat hindlimb or hyperinsulinemic euglycemic clamp (10 mU/min/kg x 2hrs) with simultaneous local, hindleg AII infusion. AII-mediated vasoconstriction was significantly (p<0.05) greater in HS-fed rats during hindlimb perfusion compared to NS (2.5-fold, 2.2-fold and1.8-fold at 1, 3 and 10nM AII, respectively). Locally infused AII (5nM) into one hindleg (retrograde via epigastric artery) of NS-fed rats was initiated 15min prior to hyperinsulinemic euglycemic clamps and did not alter insulin-mediated changes in femoral artery blood flow, microvascular perfusion or muscle glucose uptake when compared to the contralateral leg. Following dietary intervention alone, HS-fed rats had impaired insulin-mediated microvascular and metabolic actions in muscle. Local AII infusion in HS-fed rats did not alter femoral artery responses to insulin, but further impaired insulin-stimulated microvascular perfusion (1.3-fold, p=0.022) and muscle glucose uptake (1.5-fold, p=0.001) compared to the contralateral leg. We conclude that i) HS feeding augments muscle vascular sensitivity to AII and ii) local AII infusion does not acutely cause microvascular or metabolic insulin resistance in muscle, but can worsen insulin resistance during HS intake. These data suggest that insulin resistance that is specifically associated with increased dietary sodium may be ameliorated by AII blockade