Rat amylin-(8-37) enhances insulin action and alters lipid metabolism in normal and insulin-resistant rats
| Autor: | Stuart M. Furler, Edward W. Kraegen, Manthinda Hettiarachchi, Yee Soon Choong, Simon M Chalkley, Garth J. S. Cooper, Manfred Heller |
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| Předmět: |
Blood Glucose
Glycerol Male Amyloid endocrine system medicine.medical_specialty endocrine system diseases Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Amylin macromolecular substances Fatty Acids Nonesterified In Vitro Techniques Biology Insulin resistance Reference Values Physiology (medical) Internal medicine medicine Hyperinsulinemia Animals Humans Insulin Rats Wistar Muscle Skeletal Glycogen synthase Triglycerides Pancreatic hormone Human Growth Hormone Drug Synergism Lipid metabolism Glucose clamp technique medicine.disease Peptide Fragments Islet Amyloid Polypeptide Rats Endocrinology Liver Glucose Clamp Technique biology.protein Regression Analysis Acyl Coenzyme A Insulin Resistance |
| Zdroj: | Europe PubMed Central |
| Popis: | 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-[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. |
| Databáze: | OpenAIRE |
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