PREVENTING HYPERPHAGIA NORMALIZES 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE-ACTIVITY IN SMALL-INTESTINE AND LIVER OF DIABETIC RATS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 23  (6) , 831-838
Abstract
Rats with streptozotocin-induced diabetes stop growing, develop high cholesterol and triacylglycerol levels in plasma and have decreased activity of the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase (EC 1.1.1.34), in liver and increased activity in small intestine. They also eat more than normal. To determine the contribution of hyperphagia to these changes in lipid metabolism, intake of chow was restricted to the amount eaten ad lib by normal rats. Rats were meal-fed for 8 or 22 days from the time diabetes was induced. This regimen normalized reductase activity in both liver and intestine at mid-dark and mid-light and all but eliminated high plasma cholesterol and triacylglycerol levels, although plasma insulin remained low and glucose remained high. Activation of hepatic reductase by endogenous phosphatase in vitro was reduced in hyperphagic diabetic rats, but was normal in diabetic rats eating a normal amount of food. Hyperphagia, rather than direct effects of insulin deficiency as is usually assumed, is apparently responsible for perturbations of lipid metabolism in chronically diabetic rats. Hyperphagia may increase the input of dietary and newly synthesized cholesterol from the small intestine and this increased input may raise plasma cholesterol level and inhibit reductase activity in liver.