REDUCED HEPATIC STEROL CARRIER PROTEIN-2 EXPRESSION IN THE STREPTOZOTOCIN-TREATED DIABETIC RAT

While a strong relationship between the hypercholesterolemia of diabet es and premature atherosclerosis is established, the etiology for the elevation in serum cholesterol in this disease is unknown. To determin e whether diabetic hypercholesterolemia may be related to alterations in hepatic cholesterol transport capacity, sterol carrier protein-2 (S CP2) expression was examined in rats treated with streptozotocin (SZT) . Furthermore, this study examined whether 17 beta-estradiol and insul in confer a protective effect on liver cholesterol homeostasis by main taining hepatic SCP2 levels. SCP2 protein and mRNA expression were exa mined 13 days following SZT-induced diabetes onset and in diabetic rat s treated with estradiol (1 cm silastic implant) or insulin (12 units/ day). Data indicate that SCP2 protein levels were significantly reduce d in the diabetic animals and that SCP2 protein expression in the live r was inversely related to the level of serum cholesterol in the diabe tic animals. In contrast, SCP2 mRNA levels examined by slot blot, ribo nuclease protection assay, and Northern blot analysis were significant ly elevated. Both insulin and estradiol were able to enhance the expre ssion of SCP2 protein in the liver following SZT treatment The results of this investigation clearly indicate that hepatic SCP2 protein leve ls are significantly altered in the diabetic state suggesting that cho lesterol transport capacity is reduced in the SZT-treated diabetic rat The inverse relationship between serum cholesterol and hepatic SCP2 p rotein content suggests that the reduction in this protein may be a co ntributing factor in diabetic hypercholesterolemia.