Rat amylin 8-37 enhances insulin action and alters lipid metabolism
in normal and insulin resistant rats.
Hettiarachchi, M., S. Chalkley, S. M. Furler, Y-S. Choong, M. Heller,
G. J. S. Cooper, and E. W. Kraegen.
Garvan Institute of Medical Research, Sydney, Australia, School of
Biological Sciences
APStracts 4:0159E, 1997.
To clarify roles of amylin, we investigated metabolic responses to rat
amylin8-37, 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 amylin8
-37 (0.125 [mu]M/kg.h), over 5.75h. At 3.75h a hyperinsulinemic (100
mU/l) clamp with bolus 3H-2-deoxyglucose & 14C-glucose was started.
hGH infusion led to prompt (2-3 fold) basal hyperamylinemia ( p<
0.02) and hyperinsulinemia. Amylin8-37 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.
Amylin8-37 corrected hGH-induced liver insulin resistance, increased
basal plasma triglycerides and lowered plasma NEFA 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,
amylin8-37 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) Amylin8-37
increases whole body and muscle insulin sensitivity and consistently
reduces basal insulin levels in normal and hGH-induced insulin
resistant rats. 3) Amylin8-37 elicits a significant alteration of in
vivo lipid metabolism. These findings support a role of amylin in
modulating insulin action and suggest this could be mediated by
effects on lipid metabolism.
Received 23 May 1997; accepted in final form 3 July 1997.
APS Manuscript Number E237-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 24 July 1997