Summary
Peripheral hyperinsulinaemia usually found in conventionally treated Type 1 (insulin-dependent) diabetic patients may have deleterious metabolic effects. We have used a hyperinsulinaemic model to examine intermediary metabolism in two key peripheral tissues, aorta and muscle. Nine pigs were immunized with crystalline insulin. Subsequently, they showed an insulin-binding capacity of 86.2±25.0 pmol/l and fasting total serum insulin of 3.9±3.1 nmol/l (control range 0.034–0.072 nmol/l), impaired glucose tolerance after oral glucose tolerance testing, significantly elevated levels of peripheral venous serum free insulin and C-peptide, and increased mean post-prandial free insulin/glucose ratios. The immunized pigs showed marked elevation of aorta and muscle triglycerides compared with control pigs (n = 15) but similar levels of non-esterified fatty acids. The glucose-6-phosphate-dehydrogenase, malic enzyme and 3-hydroxyacyl-CoA-dehydrogenase activities were all increased significantly (by 50%–300%) in both aorta and muscle. Phosphofructokinase was decreased in both tissues. Hexokinase was increased in muscle alone whereas pyruvate kinase was significantly decreased in aorta. Glyceraldehyde-3-phosphate dehydrogenase activity was not significantly different in aorta and muscle. Thus in insulin immunized pigs with normal β-cell function and pronounced peripheral hyperinsulinaemia there was increased peripheral lipogenic activity. These findings have potentially important implications with regard to macrovascular disease in diabetes.
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Falholt, K., Alberti, K.G.M.M. & Heding, L.G. Aorta and muscle metabolism in pigs with peripheral hyperinsulinaemia. Diabetologia 28, 32–37 (1985). https://doi.org/10.1007/BF00276997
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DOI: https://doi.org/10.1007/BF00276997