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Rat amylin-(8-37) enhances insulin action and alters lipid metabolism in normal and insulin-resistant rats


To clarify roles of amylin, we investigated metabolic responses to rat amylin-(8-37), a specific amylin antagonist, in normal and insulin-resistant, human growth hormone (hGH)-infused rats. Fasting conscious rats were infused with saline or hGH, each with and without amylin-(8-37) (0.125 mumol/h), over 5.75 h. At 3.75 h, a hyperinsulinemic (100 mU/l) clamp with bolus 2-deoxy-D-[3H]glucose and [14C]glucose was started. hGH infusion led to prompt (2- to 3-fold) basal hyperamylinemia (P < 0.02) and hyperinsulinemia. Amylin-(8-37) reduced plasma insulin (P < 0.001) and enhanced several measures of whole body and muscle insulin sensitivity (P < 0.05) in both saline- and hGH-infused rats. Amylin-(8-37) corrected hGH-induced liver insulin resistance, increased basal plasma triglycerides and lowered plasma nonesterified fatty acids in both groups, and reduced muscle triglyceride and total long-chain acyl-CoA content in saline-treated rats (P < 0.05). In isolated soleus muscle, amylin-(8-37) blocked amylin-induced inhibition of glycogen synthesis but had no effect in the absence of amylin. Thus 1) hyperamylinemia accompanies insulin resistance induced by hGH infusion; 2) amylin-(8-37) increases whole body and muscle insulin sensitivity and consistently reduces basal insulin levels in normal and hGH-induced insulin resistant rats; and 3) amylin-(8-37) elicits a significant alteration of in vivo lipid metabolism. These findings support a role of amylin in modulating insulin action and suggest that this could be mediated by effects on lipid metabolism.

Type Journal
ISBN 0002-9513 (Print)
Authors Hettiarachchi, M.;Chalkley, S.;Furler, S. M.;Choong, Y. S.;Heller, M.;Cooper, G. J.;Kraegen, E. W. :
Responsible Garvan Author Prof Edward Kraegen
Publisher Name Am J Physiol
Published Date 1997-01-01
Published Volume 273
Published Issue 5 Pt 1
Published Pages E859-67
Status Published in-print
URL link to publisher's version