Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat liver sterol carrier protein (SCP) is a major intracellular protein regulating lipid metabolism and transport. During a dark-light cycle, SCP undergoes a dramatic diurnal variation in synthesis and level, reflecting translational events. Several hormones participate in the control of SCP synthesis. Insulin was implicated when the circadian rhythm of SCP was lost in both diabetes and fasting, states where insulin is low. After a 12-h fast the amplitude of the diurnal rhythm is diminished; after a 48-h fast it disappears, although SCP synthesis and level remain high. When endogenous insulin secretion is increased in fasted rats by glucose administration, SCP increases 2-fold in less than 30 min. When food intake is manipulated, but the dark-light cycle is unchanged, the circadian rhythm of SCP corresponds to feeding patterns and not light cycling. During feeding, increases in SCP are triggered following the expected increase in serum insulin. However, SCP is rapidly and significantly elevated in response to insulin only when glucocorticoids are normally high or increased by injection of the synthetic glucocorticoid, dexamethasone. Hepatocyte SCP levels are also induced by a combination of insulin and dexamethasone (2.3-fold) or insulin alone (1.3-fold). Dexamethasone alone causes a striking depression of SCP (2.4-fold). Thus, insulin is a major regulator of the diurnal variation of SCP synthesis. Glucocorticoids and other hormones (e.g. triiodothyronine) are also essential for maximum induction of SCP but play permissive roles.
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PMID:Hormonal triggering of the diurnal variation of sterol carrier protein. 351 Oct 56

Sterol carrier protein-2 (SCP2) is a 13.2-kilodalton protein that has been implicated in intracellular cholesterol transport, whereas a related sterol carrier protein, sterol carrier protein-X (SCPx; 58 kilodaltons) has been suggested to function also in the beta-oxidation of fatty acids. Although diabetes-related hyperlipidemia and altered cholesterol metabolism have been extensively studied, the intracellular cholesterol transport capacity during hyperglycemic states has not been examined. The fact that beta-oxidation is increased in diabetes whereas hepatic cholesterol metabolism is reduced suggests that differential expression of these sterol carrier proteins may accompany diabetic dyslipidemia. In this study, SCP2 protein levels were reduced by 60% in mildly hypercholesterolemic (cholesterol, > 130 and < 150 mg/dl; P < 0.01) diabetic rats and by 90% in severely hypercholesterolemic (cholesterol, > 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 SCP2 was inversely related to serum cholesterol levels. Hepatic SCP messenger RNA levels examined by ribonuclease protection assay demonstrated that hepatic SCP messenger RNA was increased 2-fold in diabetic animals. Northern blot analysis indicated that both the 0.8-kilobase SCP2-specific and the 2.1-kilobase SCPx-specific transcripts increased after STZ injection. SCPx protein induction preceded the decline in SCP2 by 4-5 days. Insulin treatment reversed the increase in SCPx and prevented the decline in SCP2. We conclude that SCP2 and SCPx are differentially expressed in the STZ-diabetic rat and suggest that this change in SCP expression should be considered a potential contributing mechanism through which cholesterol metabolism may be altered in diabetes.
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PMID:Differential expression of hepatic sterol carrier proteins in the streptozotocin-treated diabetic rat. 762 71

Reproductive dysfunction in the diabetic female rat is associated with impaired folliculogenesis, reduced corpus luteum progesterone output, and spontaneous abortion. The underlying mechanism for reduced steroid production remains unresolved. In this study we examined whether or not diabetes alters levels of P450 side-chain cleavage enzyme (P450scc), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), or the cholesterol transport proteins, steroidogenic acute regulatory (StAR) protein and sterol carrier protein-2 (SCP2), leading to lower progesterone levels and pregnancy loss. Rats (Day 3 pregnant) received an injection of streptozotocin (STZ, 60 mg/kg; i.v.) to induce a diabetic state; P450scc, 3 beta-HSD, and SCP2 were examined by Western and Northern blot analysis in ovarian tissue 12 days after injection of STZ (diabetic rats, n = 12) or vehicle (nondiabetic rats, n = 12). Serum progesterone, triglyceride, and beta-hydroxybutyrate (beta-HBA) levels were also examined. Results indicate that diabetic rats that aborted (diabetic-fetus [Ft], n = 6) had significantly lower progesterone levels (7.04 +/- 2.6 ng/ml; p < 0.004) than nondiabetic animals (108.6 +/- 5.15 ng/ml) and diabetic +Ft animals (74.3 +/- 8.9 ng/ml, n = 6). Western blot analysis of ovarian P450scc and 3 beta-HSD in the nondiabetic rats and the diabetic rats with fetuses indicated no significant difference. In contrast, ovaries from diabetic animals without fetuses had significantly lower SCP2 levels (p < 0.017) compared to controls. Concomitant with the reduction in SCP2, a 58-kDa SCP2-immunoreactive protein, referred to as sterol carrier protein-X (SCPx), increased significantly (p < 0.001). The C-terminal sequence of SCPx is identical to SCP2, while its N-terminal region is homologous with 3-oxoacyl coenzyme A thiolase, an enzyme involved in fatty acid metabolism. Increased SCPx expression coincided with increased serum triglyceride and beta-HBA levels, suggesting that the enhanced SCPx level may coincide with an ovarian shift to fatty acid metabolism. When SCPx steady-state mRNA levels were measured using an SCPx-specific riboprobe (280-bp protected fragment) in a ribonuclease protection assay, ovarian SCPx mRNA levels in the diabetic animals were increased 4.2-fold compared to control SCPx mRNA levels. Ovarian StAR mRNA levels were increased slightly in the diabetic animals, and ovarian P450scc and 3 beta-HSD mRNA levels were increased 3-fold in the diabetic animals that aborted relative to the nondiabetic animals and the +Ft diabetic animals. Results of this study confirm that SCPx mRNA levels are elevated following diabetes onset and that StAR, P450scc, and 3 beta-HSD mRNA levels do not correspond with the reduced steroid hormone profile associated with diabetes. These results are concordant with the possibility that reduced steroid levels in the diabetic animals reflect a loss of SCP2-mediated cholesterol transport capacity as SCPx/3-oxoacyl coenzyme A thiolase expression is enhanced.
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PMID:Altered ovarian sterol carrier protein expression in the pregnant streptozotocin-treated diabetic rat. 879 56