Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein-lipase activity was determined in tissue from the skeletal muscle of the leg and the subcutaneous adipose tissue of the abdomen in fourteen patients before and after 1 month of clofibrate administration. The concentrations of serum triglycerides decreased by, on the average, 37% in a group of thirteen patients which mainly consisted of subjects with type-IV hyperlipoproteinaemia. Clofibrate administration was associated with an average increase of the skeletal muscle-tissue lipoprotein-lipase activity of 50% (P less than 0.005). There was a significant correlation between the percentage changes in skeletal muscle-tissue lipoprotein-lipase activity and those of the triglycerides concentrations and the K2-values in an intravenous fat tolerance test during clofibrate treatment. Adipose-tissue lipoprotein-lipase activity did not change significantly. One patient with type-I hyperlipoproteinaemia had very low values of skeletal muscle-tissue lipoprotein-lipase activity and moderately low adipose-tissue lipoprotein-lipase activity. In this patient, neither the tissue lipoprotein-lipase activity nor the triglycerides concentration changed during clofibrate therapy. Fasting serum insulin concentrations decreased significantly during clofibrate administration and the percentage decrease was significantly correlated to the percentage increase of skeletal-muscle lipoprotein-lipase activity. It is suggested that the lowering of insulin levels is a possible mechanism through which glucagon activity is enhanced and this may increase skeletal muscle-tissue lipoprotein-lipase activity.
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PMID:Increase of the lipoprotein-lipase activity in human skeletal muscle during clofibrate administration. 41 37

Arginine-induced insulin and glucagon secretion preceding and following clofibrate treatment was studied in 13 patients with endogenous hypertriglyceridemia. A positive correlation was demonstrated between fasting insulin and triglyceride levels and between the fasting insulin/glucagon molar ratio and triglyceride levels. In patients with endogenous hypertriglyceridemia, anginine infusion induced a significantly increased glucagon response with respect to that found in controls. No correlation was found to exist between glucagon and free fatty acids (FFA) or between glucagon and triglyceride levels. The same lack of correlation was found in normal subjects rendered hypertriglyceridemic by means of Intralipid infusion, which did not modify the fasting glucagon-like immunoreactivity (GLI) or the GLI response to arginine. Clofibrate treatment induces a triglyceride reduction (incrementTG) which is correlated with the reduction in the insulin/glucagon molar ration (incrementI/G). After clofibrate treatment there is also a significant reduction in fasting GLI levels and in the insulin response to arginine, and an increase in the glucagon response. Clofibrate could exercise its hypolipidemic effect by modifying the relationship between insulin and glucagon levels.
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PMID:Glucagon secretion in primary endogenous hypertriglyceridemia before and after clofibrate treatment. 114 89

Prostaglandins (PG) modulate hepatocyte glucose and lipid metabolism. Hepatocytes rapidly metabolize PG via beta-oxidation, terminating PG action. Clofibrate induces hepatic peroxisomal beta-oxidative activity, for which PG are substrates. To determine the effect of clofibrate-treatment on liver PG metabolism and action, hepatocytes were isolated from rats maintained on a control or clofibrate-supplemented (0.5%) diet for 7 to 9 days. Rates of PG catabolism were determined by high performance liquid chromatography resolution of [3H]PG from [3H]metabolites. Clofibrate treatment enhanced the rates of PGE2, PGF2, and PGD2 degradation by 85%, 278% and 137%, respectively. Rates of PG degradation were correlated with hepatocyte carnitine acetyltransferase activity, a marker of peroxisomal proliferation. Further evidence of enhanced hepatocyte peroxisomal beta-oxidation of PG after clofibrate-treatment was obtained by confirming loss of the 1-position carbon from [1-14C]PGE2 during PGE2 metabolism and failure of the carnitine acyltransferase inhibitor acetyl-DL-aminocarnitine to inhibit PGE2 metabolism. Associated with the faster degradation of PGE2 by hepatocytes from clofibrate-treated rats was loss of inhibition of hepatocyte glucagon-stimulated glycogenolysis by exogenous PGE2. Thus, clofibrate's induction of peroxisomal beta-oxidation is associated with accelerated catabolism of PG and decreased PG action. Alterations in PG breakdown provide a mechanism for modulating hepatic PG effects.
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PMID:Effect of clofibrate treatment on hepatic prostaglandin catabolism and action. 204 19

Clofibrate induces hypertrophy and hyperplasia and marked changes in the activities of various enzymes in rat liver. We examined the effects of treatment of rats with clofibrate on enzyme induction and on rates of metabolic flux in hepatocytes isolated from the periportal and perivenous zones of the liver. Clofibrate induced the activities of carnitine acetyltransferase (90-fold), carnitine palmitoyltransferase (3-fold) and NADP-linked malic enzyme (3-fold) to the same level in periportal as in perivenous hepatocytes, suggesting that these enzymes were induced uniformly throughout the liver acinus. Increased rates of palmitate metabolism and ketogenesis after clofibrate treatment were associated with: a more oxidised mitochondrial redox state; diminished responsiveness to glucagon and loss of periportal/perivenous zonation. Despite the marked liver enlargement and hyperplasia caused by clofibrate, the normal periportal/perivenous zonation of alanine aminotransferase and gluconeogenesis was preserved in livers of clofibrate-treated rats, indicating that clofibrate-induced hyperplasia does not disrupt the normal acinar zonation of these metabolic functions.
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PMID:Clofibrate induces carnitine acyltransferases in periportal and perivenous zones of rat liver and does not disturb the acinar zonation of gluconeogenesis. 277 85

1. The role of endogenous glucagon and insulin on the hypolipidemic and glycogenolytic effect of clofibrate was determined in the euthyroid and propylthiouracil (PTU)-induced hypothyroid mice. 2. PTU was fed in diet (0.15%) for 2 weeks and then clofibrate added to diet (0.25%) for 4 weeks. 3. Both PTU and clofibrate significantly increased liver weight but had no effect on kidney weight. PTU significantly decreased plasma triglycerides (TG) and increased cholesterol (Ch). 4. Clofibrate had a significant hypotriglyceridemic effect in both euthyroid and hypothyroid mice but did not affect plasma cholesterol. 5. Clofibrate decreased hepatic glycogen in euthyroid but not in hypothyroid mice. 6. Glucose-6-phosphatase activity was not affected by either PTU or clofibrate. 7. Neither PTU nor clofibrate affected hepatic TG or Ch. 8. Biliary lipid changes due to PTU treatment were reversed by clofibrate administration. 9. Since plasma insulin and glucagon levels were not affected by clofibrate in either euthyroid or hypothyroid mice, our results suggest that the hypotriglyceridemic and glycogenolytic effect of clofibrate is not mediated by changes in circulating insulin and glucagon ratio. 10. Moreover, while the glycogenolytic effect of clofibrate seems to be dependent, the hypotriglyceridemic effect seems to be independent of thyroid hormones.
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PMID:Hypolipidemic and glycogenolytic effect of clofibrate (CPIB) in hypothyroid mice: role of insulin and glucagon. 703 29