DIFFERENTIAL EXPRESSION OF HEPATIC STEROL CARRIER PROTEINS IN THE STREPTOZOTOCIN-TREATED DIABETIC RAT

Sterol carrier protein-2 (SCP2) is a 13.2-kilodalton protein that has been implicated in intracellular cholesterol transport, whereas a rela ted sterol carrier protein, sterol carrier protein-X (SCPx; 58 kilodal tons) has been suggested to function also in the beta-oxidation of fat ty acids. Although diabetes-related hyperlipidemia and altered choles terol metabolism have been extensively studied, the intracellular chol esterol transport capacity during hyperglycemic states has not been ex amined. The fact that beta-oxidation is increased in diabetes whereas hepatic cholesterol metabolism is reduced suggests that differential e xpression of these sterol carrier proteins may accompany diabetic dysl ipidemia. In this study, SCP2 protein levels were reduced by 60% in mi ldly hypercholesterolemic (cholesterol, >130 and <150 mg/dl; P < 0.01) diabetic rats and by 90% in severely hypercholesterolemic (cholestero l, >150 mg/dl; P < 0.002) diabetic animals. In contrast, hepatic SCPx protein expression increased (3.5-fold) after diabetes induction with streptozotocin (STZ). The decline in SCPB was inversely related to ser um cholesterol levels. Hepatic SCP messenger RNA levels examined by ri bonuclease protection assay demonstrated that hepatic SCP messenger RN A was increased 2-fold in diabetic animals. Northern blot analysis ind icated that both the 0.8-kilobase SCP2-specific and the 2.1-kilobase S CPx-specific transcripts increased after STZ injection. SCPx protein i nduction preceded the decline in SCP2 by 4-5 days. Insulin treatment r eversed the increase in SCPx and prevented the decline in SCP2. We con clude that SCP2 and SCPx are differentially expressed in the STZ-diabe tic rat and suggest that this change in SCP expression should be consi dered a potential contributing mechanism through which cholesterol met abolism may be altered in diabetes.