Abstract

Elevated serum cholesterol levels and an increase in cardiovascular events are frequently seen in diabetes. We used microarray and RT‐PCR analysis to investigate the expression of key hepatic genes in the male Sprague‐Dawley rat, a predominantly HDL animal, in which diabetes was induced by injection of 65 mg/kg of streptozotocin. As expected, HMG‐CoA reductase, glucokinase, fatty acid synthase, acetyl CoA carboxylase, stearoyl CoA desaturase, pyruvate kinase and thyroid hormone responsive protein expression was decreased. On the other hand, expression of serine dehydratase, carnitine palmitoyl transferase, carnitine acetyltransferase, insulin‐like growth factor binding protein‐1, INSIG‐1 and 2, PPAR gamma coactivator 1 alpha, and ABCC‐3 was increased in the diabetic rats. The expression of scavenger receptor B 1 and Apo A‐I were increased about 3‐fold in the streptozotocin‐induced diabetic animals. This may be a consequence of the severe insulin deficiency which promotes robust lipolysis. These genes are critical to reverse cholesterol transport. Consistent with these findings, a decrease in hepatic scavenger receptor B 1 has been reported in an animal model of Type 2 diabetes with increased insulin levels. (This investigation was supported by NIH grant DK075414).

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