Aorta and muscle metabolism in pigs with peripheral hyperinsulinaemia.
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 beta-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.
D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002417:Cattle; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006946:Hyperinsulinism / Q000201:enzymology / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D009132:Muscles / Q000201:enzymology / Q000378:metabolism*; D013552:Swine; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides