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

Abstract

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.

• Authors: M Hettiarachchi, S Chalkley, S M Furler, Y S Choong, M Heller, G J Cooper, E W Kraegen
• Journal: The American journal of physiology (Am J Physiol) Vol. 273 Issue 5 Pg. E859-67 (11 1997) ISSN: 0002-9513 [Print] United States
• PMID: 9374670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acyl Coenzyme A
• Amyloid
• Blood Glucose
• Fatty Acids, Nonesterified
• Insulin
• Islet Amyloid Polypeptide
• Peptide Fragments
• Triglycerides
• amylin (8-37)
• Human Growth Hormone
• Glycerol

Topics

• Acyl Coenzyme A (metabolism)
• Amyloid (antagonists & inhibitors, blood, pharmacology)
• Animals
• Blood Glucose (drug effects, metabolism)
• Drug Synergism
• Fatty Acids, Nonesterified (blood)
• Glucose Clamp Technique
• Glycerol (blood)
• Human Growth Hormone (pharmacology)
• Humans
• In Vitro Techniques
• Insulin (blood, pharmacology)
• Insulin Resistance
• Islet Amyloid Polypeptide
• Liver (drug effects, physiology)
• Male
• Muscle, Skeletal (drug effects, physiology)
• Peptide Fragments (pharmacology)
• Rats
• Rats, Wistar
• Reference Values
• Regression Analysis
• Triglycerides (blood, metabolism)