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

• Published in: American journal of physiology: endocrinology and metabolism Vol. 273; no. 5; pp. E859 - E867
• Main Authors: Hettiarachchi, M, Chalkley, S, Furler, S.M, Choong, Y.S, Heller, M, Cooper, G.J.S, Kraegen, E.W
• Format: Journal Article
• Language: English
• Published: United States 01.11.1997
• Subjects: Acyl Coenzyme A - metabolism; Amyloid - antagonists & inhibitors; Amyloid - blood; Amyloid - pharmacology; Animals; Blood Glucose - drug effects; Blood Glucose - metabolism; CANARD; Drug Synergism; DUCKS; Fatty Acids, Nonesterified - blood; Glucose Clamp Technique; Glycerol - blood; Human Growth Hormone - pharmacology; Humans; In Vitro Techniques; Insulin - blood; Insulin - pharmacology; Insulin Resistance; Islet Amyloid Polypeptide; Liver - drug effects; Liver - physiology; Male; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiology; PATO; Peptide Fragments - pharmacology; Rats; Rats, Wistar; Reference Values; Regression Analysis; Triglycerides - blood; Triglycerides - metabolism
• ISSN: 0002-9513; 0193-1849; 2163-5773; 1522-1555
• DOI: 10.1152/ajpendo.1997.273.5.E859

1  Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; and 2  School of Biological Sciences and 3  Department of Medicine, School of Medicine, University of Auckland, Auckland 1, New Zealand 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 µmol/h), over 5.75 h. At 3.75 h, a hyperinsulinemic (100 mU/l) clamp with bolus 2-deoxy- D -[ 3 H]glucose and [ 14 C]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. human growth hormone; euglycemic clamp; muscle; liver; triglycerides; long-chain acyl-CoA