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)

After enteral administration of 200 mg/kg alpha-hexachlorocyclohexane (alpha-HCH) female Wistar rats develop a hyperlipemia. 48 h after administration of alpha-HCH, serum triglycerides are increased by 300%, whereas both serum cholesterol and serum total phospholipids only increase by about 45%. Serum free fatty acids are not significantly altered. Fractionation of the serum lipoproteins by ultracentrifugation shows that the hyperlipemia is due to a fivefold increase in serum very low density lipoproteins. Hepatic triglyceride secretion, calculated after i.v. injection of Triton WR 1339, is increased in animals pretreated wtih alpha-HCH. Corresponding to this observation, drugs known to diminish the triglyceride secretion of the liver, such as actinomycin D, cycloheximide; glucagon, orotic acid, CFT 1201, and CFT 1042 reduce the alpha-HCH-induced hyperlipemia. We concluded from the results that hyperlipoproteinemia after alpha-HCH is due to an increased hepatic very low density lipoprotein secretion. At the same time, the blood sugar level was decreased in fasting animals after treatment with alpha-HCH. Earlier experiments suggest that this effect is due to a decreased gluconeogenesis in the liver.
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PMID:Increase of serum very low density lipoproteins in rats after administration of alpha-hexachlorocyclohexane. 6 95

Chronic exercise training is recognized to reduce plasma lipid levels in man and animals, but the mechanism(s) mediating this phenomenon have not been defined. In the present study, we examined triglyceride (TG) production and disposal in vivo in a genetic model of human type IV hyperlipemia, the obese Zucker rat. Utilizing the normolipemic thin littermate as the control, we investigated endogenous production of TG utilizing the Triton methodology and peripheral disposal of an exogenous lipid emulsion utilizing Intralipid injection. In the sedentary state, the hyperlipemic obese Zucker rat demonstrated a threefold elevation in triglyceride secretion rate relative to the normolipemic thin littermate. After a 3-wk period of exercise training, a reduction of basal plasma TG concentration of 42% was associated with a 51% reduction in TG secretion rate, a change adequate to account for the hypolipemic response. Moreover, chronic exercise training also improved the ability to dispose of an Intralipid load. A similar reduction in TG production with reduced TG removal was observed in the thin normolipemic rats, a result that suggests that the lipid lowering response to exercise training may be predominantly mediated by reduced secretion of TG. The possible relationship between reduced TG secretion and alterations in the bihormonal axis of insulin and glucagon are discussed.
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PMID:Reduced triglyceride secretion: a metabolic consequence of chronic exercise. 62 36

Male adult Wistar rats were fed a semipurified diet rich in sucrose (53 g/100 g diet). The effects of chronic glucagon administration (20 micrograms.day-1.rat-1, for 21 d) were studied on plasma lipid levels, triacylglycerol secretion rates and fractional catabolic rates determined by the intravenous fat tolerance test. Triacylglycerol secretion rates of plasma, chylomicron and very low density lipoprotein (VLDL) were measured by using the Triton WR 1339 method. In both fasting and postprandial states, the different rates were not significantly modified by glucagon treatment. However, in the treated animals, significantly decreased triacylglycerol concentrations were observed in plasma and VLDL during fasting (-41 and -46%, respectively) and also in chylomicrons in the postprandial state (-37%) relative to control animals. These data could be accounted for by an increased removal rate of triacylglycerol-rich lipoprotein. The estimated values of fractional rate constants (Triton WR 1339 experiment) were increased for VLDL (+62%) in the fasting state and for chylomicrons (+104%) in the postprandial state. Similarly, the fractional catabolic rate determined with the intravenous fat tolerance test (Intralipid, Kabivitrum, Sweden) was increased 49% by glucagon treatment, suggesting an effect of glucagon on the catabolism of triacylglycerol-rich lipoproteins. Glucagon treatment did not modify the composition of VLDL obtained 60 min after Triton WR 1339 injection, except that in the fasting state apo B100 proportions and concentrations increased, suggesting a specific effect on the hepatic secretion of apo B100 VLDL.
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PMID:Effect of chronic glucagon administration on the metabolism of triacylglycerol-rich lipoproteins in rats fed a high sucrose diet. 199 54

Effects on insulin release, cyclic AMP content and protein phosphorylation of agents modifying cyclic AMP levels have been tested in intact rat islets of Langerhans. Insulin release induced by glucose was potentiated by dibutyryl cyclic AMP, glucagon, cholera toxin and 3-isobutyl-1-methylxanthine (IBMX); the calmodulin antagonist trifluoperazine reversed these potentiatory effects. Inhibition by trifluoperazine of IBMX-potentiated release was, however, confined to concentrations of IBMX below 50 microM; higher concentrations, up to 1 mM, were resistant to inhibition by trifluoperazine. IBMX-potentiated insulin release was also inhibited by 2-deoxyadenosine, an inhibitor of adenylate cyclase. In the absence of glucose, IBMX at concentrations up to 1 mM did not stimulate insulin release and in the presence of 3.3 mM-glucose IBMX was effective only at a concentration of 1 mM; under the latter conditions trifluoperazine again did not inhibit insulin secretion. The maximum effect on insulin release was achieved with 25 microM-IBMX. Islet [cyclic AMP] was increased by IBMX, with the maximum rise occurring with 100 microM-IBMX. The increase in [cyclic AMP] elicited by IBMX was more rapid than that induced by cholera toxin. Trifluoperazine did not significantly affect islet cyclic AMP levels under any of the conditions tested. When islets were incubated with [32P]Pi, radioactivity was incorporated into islet ATP predominantly in the gamma-position. The rate of equilibration of label was dependent on medium Pi and glucose concentration and at optimal concentrations of these 100% equilibration of internal [32P]ATP with external [32P]Pi required a period of 3h. Radioactivity was incorporated into islet protein and, in response to an increase in islet [cyclic AMP], the major effect was on a protein of Mr 15 000 on sodium dodecyl sulphate/polyacrylamide gels. The extent of phosphorylation of the Mr-15 000 protein was correlated with the level of cyclic AMP: phosphorylation in response to IBMX was inhibited by 2-deoxyadenosine but not by trifluoperazine. Fractionation of islets suggested that the Mr-15 000 protein was of nuclear origin: the protein co-migrated with histone H3 on acetic acid/urea/Triton gels. In the islet cytosol a number of proteins were phosphorylated in response to elevation of islet [cyclic AMP]: the major species had Mr values of 18 000, 25 000, 34 000, 38 000 and 48 000. Culture of islets with IBMX increased the rate of [3H]-thymidine incorporation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cyclic AMP-dependent protein phosphorylation and insulin secretion in intact islets of Langerhans. 620 Nov 63

The formation of hepatic bile requires that water be transported across liver epithelia. Rat hepatocytes express three aquaporins (AQPs): AQP8, AQP9, and AQP0. Recognizing that cholesterol and sphingolipids are thought to promote the assembly of proteins into specialized membrane microdomains, we hypothesized that canalicular bile secretion involves the trafficking of vesicles to and from localized lipid-enriched microdomains in the canalicular plasma membrane. Hepatocyte plasma membranes were sonicated in Triton and centrifuged overnight on a sucrose gradient to yield a Triton-soluble pellet and a Triton-insoluble, sphingolipid-enriched microdomain fraction at the 5%/30% sucrose interface. The detergent-insoluble portion of the hepatocyte plasma membrane was enriched in alkaline phosphatase (a microdomain-positive marker) and devoid of amino-peptidase N (a microdomain-negative marker), enriched in caveolin, both AQP8 and AQP9, but negative for clathrin. The microdomain fractions contained chloride-bicarbonate anion exchanger isoform 2 and multidrug resistance-associated protein 2. Exposure of isolated hepatocytes to glucagon increased the expression of AQP8 but not AQP9 in the microdomain fractions. Sphingolipid analysis of the insoluble fraction showed the predominant species to be sphingomyelin. These data support the presence of sphingolipid-enriched microdomains of the hepatocyte membrane that represent potential localized target areas for the clustering of AQPs and functionally related proteins involved in canalicular bile secretion.
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PMID:Membrane microdomains in hepatocytes: potential target areas for proteins involved in canalicular bile secretion. 1583 30

Canalicular bile is formed by the osmotic filtration of water in response to osmotic gradients generated by active transport at the apical and basolateral plasma membrane domains of hepatocytes. We recently demonstrated that mixed plasma membrane fractions isolated from rat hepatocyte couplets contain lipid microdomains ("rafts") enriched in cholesterol and sphingolipids and AQP8 and 9. We isolated lipid microdomains from hepatocyte apical and basolateral plasma membrane domains using Triton X-100 as detergent, and characterized their lipid and protein composition. A Triton-insoluble band ("raft fraction") at the 5%/30% sucrose interface in both apical and basolateral fractions was enriched for alkaline phosphatase (apical) and Na/K ATPase (basolateral) and was negative for amino peptidase-N. This detergent-insoluble band was also positive for caveolin-1 (a "raft" associated protein) and negative for clathrin (a "raft" negative protein). Lipid analysis showed that, the Triton-insoluble fraction was highly enriched in cholesterol and sphingolipids. Immunofluorescence staining on hepatocyte couplets for both caveolin-1 and cholera toxin B showed a punctate distribution on both the apical and basolateral plasma membranes, consistent with localized membrane microdomains. Dot blot analysis showed that the "raft" associated ganglioside GM1 was enriched in the detergent-insoluble fraction both domains. Furthermore, exposure of isolated hepatocytes to glucagon, a choleretic agonist, significantly increased the expression of AQP8 associated with the apical microdomain fractions but had no effect on AQP9 expression in the basolateral microdomain fractions. In conclusion, "rafts" represent target microdomains for exocytic insertion and retrieval of "flux proteins", including AQPs, involved in canalicular bile secretion.
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PMID:Isolation and characterization of lipid microdomains from apical and basolateral plasma membranes of rat hepatocytes. 1644 Mar 38