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)

In the rat, the suckling-weaning transition is accompanied by marked changes in nutrition. During the suckling period, the pups are fed with milk which is a high-fat low-carbohydrate diet. At weaning, milk is progressively replaced by the rat chow which is a high-carbohydrate low-fat diet. This is accompanied by considerable hormonal modifications: an increase in plasma insulin and a decrease in plasma glucagon concentrations, as well as by marked changes in metabolic pathways in liver: decrease in hepatic gluconeogenesis, increase in lipogenesis, and appearance of liver glucokinase. Most of the data concerning these changes are related to maximal activity of enzymes. The recent availability of specific cDNA probes for phosphoenolpyruvate carboxykinase, acetyl-CoA carboxylase, fatty acid synthase and glucokinase has allowed study of the role of pancreatic hormones and of nutrition in the changes of the expression of these genes at weaning in the rat.
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PMID:Hormonal control of specific gene expression in the rat liver during the suckling-weaning transition. 197 92

Hepatic fatty acid synthase is regulated by nutritional state. Starvation decreases and refeeding increases the activity of avian fatty acid synthase, principally by regulating transcription of the gene (Back, B. W., Goldman, M. J., Fisch, J.E., Ochs, R.A., and Goodridge, A.G. (1986) J. Biol. Chem. 261, 4190-4197). In chick embryo hepatocytes in culture, the stimulatory effect of feeding on fatty acid synthase activity is mimicked by adding triiodothyronine and insulin; the inhibitory effect of starvation is mimicked by adding glucagon or cyclic AMP. We now show that triiodothyronine alone stimulates transcription of fatty acid synthase by 4- to 6-fold, about the same as the increase in fatty acid synthase mRNA. When added alone, insulin has little or no effect on transcription, mRNA level, or enzyme activity. In combination with triiodothyronine, however, insulin amplifies the response to triiodothyronine by about 2-fold, leading to an overall increase of about 10-fold. Insulin-like growth factor 1 (IGF-1) has the same effect as insulin, no effect by itself, and amplification of the stimulation by triiodothyronine. A maximally effective dose of insulin has no effect in the presence of a maximally effective dose of IGF-1, suggesting regulation by a common pathway. It takes much less IGF-1 than insulin to achieve a given effect, suggesting that both insulin and IGF-1 may act through IGF-1 receptors. Plasma levels of IGF-1 are decreased by starvation and increased by feeding (reviewed by Froesch, E.R., and Zapf, J. (1985) Diabetologia 28, 485-493). Thus, IGF-1 may play a physiological role in the regulation of hepatic fatty acid synthase during transitions between the starved and fed states, roles previously assigned primarily to insulin and glucagon. IGF-1 regulates transcription of the fatty acid synthase gene. Insulin and IGF-1 also have similar effects on activity, mRNA abundance, and transcription of the malic enzyme gene. Glucagon or dibutyryl cyclic AMP inhibit fatty acid synthase activity and mRNA level in hepatocytes in culture by 70-80% and 60%, respectively, but have no effect on transcription of the fatty acid synthase gene, suggesting a post-transcriptional mode of regulation for cyclic AMP.
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PMID:Triiodothyronine stimulates transcription of the fatty acid synthase gene in chick embryo hepatocytes in culture. Insulin and insulin-like growth factor amplify that effect. 217 Apr 11

Acetyl-CoA carboxylase activity was measured in digitonin-permeabilized rat hepatocytes by coupling the carboxylase reaction to the fatty acid synthase reaction. Using this assay the activity of acetyl-CoA carboxylase was covariant with the rate of fatty acid synthesis. Insulin and the tumor promotor phorbol myristate acetate were found to stimulate, and glucagon and noradrenaline to inhibit both cellular parameters. The stimulation of acetyl-CoA carboxylase by insulin developed slowly (15 to 30 min) whereas the phorbol myristate acetate effect developed faster (within 15 min). The inhibition of the enzyme caused by glucagon was already apparent within 1 min after hormone addition. Inhibition by noradrenaline, in the presence of propranolol, was also quite rapid and occurred within 2 min after addition of the agonist.
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PMID:Time course of hormonal effects on acetyl-CoA carboxylase as measured in digitonin-permeabilized rat hepatocytes. 257 37

Lipogenesis in isolated fetal hepatocytes in suspension for 3 h was modulated by insulin depending on substrates utilization, but was inhibited by glucagon and noradrenaline from all substrates studied. After primary culture for 5 days in the presence of glucose, the lipogenic response to insulin increased, the glucagon response decreased and noradrenaline produced the same degree of inhibition at 3 h. At 24 h, insulin produced an even higher increase on lipogenesis parallel to an increase in fatty acid synthase activity. Dexamethasone increased lipogenesis, but progesterone had no effect. Both hormones, in the presence of insulin, increased lipogenesis and fatty acid synthase activity. Triiodothyronine, alone or in the presence of insulin, increased lipogenesis and fatty acid synthase activity.
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PMID:Rates of lipogenesis in fetal hepatocytes in suspension and in primary culture: hormonal effects. 266 43

Insulin stimulates lipogenesis by 100% for 5 h by a covalent modulation of acetyl-CoA carboxylase, and by 200% for 24 h by increasing malic enzyme and fatty acid synthase enzymic activities in brown-adipocyte primary cultures. At short times, noradrenaline and isoprenaline decrease lipogenesis. However, phenylephrine and glucagon have no effect. At long times, dexamethasone inhibits lipogenesis. This effect is precluded in the presence of insulin. Progesterone and tri-iodothyronine, alone or in the presence of insulin, produce a stimulation of the rates of lipogenesis.
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PMID:Hormonal regulation of rat foetal lipogenesis in brown-adipocyte primary cultures. 304 67

The activity of hepatic fatty acid synthase (EC 2.3.1.85) correlates positively with the rate of synthesis of long-chain fatty acids. Thus, in a starved chick, both the rate of fatty acid synthesis and the activity of fatty acid synthase are low. Feeding stimulates both processes. The increase in fatty acid synthase activity caused by feeding is due to an increase in the concentration of enzyme protein, which in turn is caused by an increase in the rate of synthesis of the enzyme. Using fatty acid synthase cDNA clones isolated in our laboratory, we showed that feeding causes a rapid increase in the level of fatty acid synthase mRNA. Increased transcription of the fatty acid synthase gene precedes the increase in fatty acid synthase mRNA level caused by feeding, which indicates regulation at the level of transcription. The feeding-induced stimulation of fatty acid synthase can be mimicked in culture by incubating chick embryo hepatocytes with insulin and thyroid hormone. Glucagon inhibits the increase caused by insulin and thyroid hormone. Enzyme synthesis is the regulated step. In hepatocytes in culture, thyroid hormone stimulates and glucagon inhibits the accumulation of fatty acid synthase mRNA. Insulin has only a small stimulatory effect on mRNA level despite a large stimulation of the synthesis of fatty acid synthase. Thus, thyroid hormone and glucagon regulate enzyme level at a pretranslational step, whereas insulin regulates the translation of fatty acid synthase mRNA. We conclude that complex hormonal regulation of the production and translation of fatty acid synthase mRNA underlies the dietary regulation of enzyme synthesis observed in intact animals. Future work will involve isolation of cloned genomic DNA for the fatty acid synthase gene and identification of nucleotide sequences involved in the regulation of this gene.
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PMID:Regulation of the gene for fatty acid synthase. 352 33

Mechanisms involved in the multihormonal regulation of fatty acid synthase have been investigated by comparing levels of its mRNA with rates of enzyme synthesis in chick embryo hepatocytes in culture. Triiodothyronine or insulin caused about a 2.5-fold increase in the relative rate of synthesis of fatty acid synthase. Together, these hormones were synergistic, stimulating enzyme synthesis by nearly 40-fold (Fischer, P.W.F., and Goodridge, A.G. (1978) Arch. Biochem. Biophys. 190, 332-344). Addition of triiodothyronine stimulated increases in mRNA levels comparable to increases in enzyme synthesis whether insulin was present or not. Thus, triiodothyronine regulates fatty acid synthase primarily by controlling the amount of its mRNA. Addition of insulin, in the presence of triiodothyronine, stimulated enzyme synthesis by 14-fold and mRNA levels by only 2-fold. In the absence of triiodothyronine, insulin had no effect on mRNA levels. Thus, insulin has a major effect on the translation of fatty acid synthase mRNA. After the addition of triiodothyronine, fatty acid synthase mRNA accumulated with sigmoidal kinetics, approaching a new steady state about 48 h after the addition of hormone. Puromycin, an inhibitor of protein synthesis, blocked the effect of triiodothyronine. We suggest that the abundances of both fatty acid synthase and malic enzyme mRNAs are regulated by a common triiodothyronine-induced peptide intermediate which has a relatively long half-life. Glucagon caused an 80% decrease in the synthesis of fatty acid synthase (Fischer, P.W.F., and Goodridge, A.G. (1978) Arch. Biochem. Biophys. 190, 332-344) and a 60% decrease in the level of fatty acid synthase mRNA. Thus, glucagon regulates fatty acid synthase by controlling the concentration of its mRNA. The synthesis of malic enzyme also was inhibited by glucagon at a pretranslational step, but the inhibition was almost complete. Thus, despite coordinated regulation of the concentrations of these enzymes during starvation and refeeding, individual hormones sometimes regulate synthesis of the two enzymes at the same step and to about the same degree and sometimes at different steps or to very different degrees.
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PMID:Hormonal regulation of lipogenic enzymes in chick embryo hepatocytes in culture. Expression of the fatty acid synthase gene is regulated at both translational and pretranslational steps. 353 37

The levels of malic enzyme and fatty acid synthase are increased by feeding and decreased by starvation in liver in vivo and are increased by triiodothyronine and decreased by glucagon in hepatocytes in culture. Cloned malic enzyme and fatty acid synthase cDNAs are being used to analyze regulation of these unique genes. Dietary regulation of both enzymes occurs at pretranslational steps. Increased transcription and increased mRNA stability contribute about equally to a 20-fold increase in malic enzyme mRNA level when starved ducklings are refed. In contrast, a 10-fold increase in the level of fatty acid synthase mRNA is largely accounted for by increased transcription of this gene. In chick-embryo hepatocytes incubated in serum-free medium containing insulin, triiodothyronine causes a greater than 10-fold increase in levels of both malic enzyme and fatty acid synthase mRNAs. Kinetic and inhibitor experiments suggest a protein intermediate in the increases of malic enzyme and fatty acid synthase mRNAs caused by triiodothyronine. For malic enzyme, the stimulation by triiodothyronine is predominantly posttranscriptional. Glucagon decreases the level of malic enzyme mRNA by 90 to 95%, with regulation occurring at a posttranscriptional step. Inhibitor experiments suggest that stimulation of the degradation of malic enzyme mRNA is partially responsible. Glucagon inhibited fatty acid synthase mRNA level by less than 50%; the inhibited step has not been identified. Thus, the coordinated regulation of malic enzyme and fatty acid synthase proteins by nutritional state may involve different hormones regulating at different points. A surprisingly large component of the regulation is posttranscriptional.
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PMID:Regulation of genes for enzymes involved in fatty acid synthesis. 354 53

In vivo and in vitro experiments strongly support the view that marked increases in the levels of mRNA and in the activities of lipogenic enzymes that occur in liver and white adipose tissue of the rat after weaning to a high-carbohydrate diet are dependent on an increase in plasma glucose and insulin concentrations. An increased glucose metabolism is necessary for the expression of insulin effects on fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) mRNA accumulation in white adipose tissue, as insulin is ineffective in vitro in the absence of glucose. It is suggested that intracellular glucose-6-phosphate could play an important role in the effect of insulin on lipogenic enzyme gene expression in white adipose tissue. Other hormones and substrates could also play a role in the surge of lipogenesis after weaning. The fall in plasma glucagon after weaning to a high-carbohydrate diet could reinforce the insulin-induced accumulation of FAS and ACC mRNA, as this hormone inhibits the accumulation of lipogenic enzyme mRNA in liver and white adipose tissue. The decrease in the dietary supply of fat after weaning to a high-carbohydrate diet could also potentiate the accumulation of FAS and ACC mRNA in liver because long-chain poly-unsaturated fatty acids are potent inhibitors of the expression of the genes encoding liver lipogenic enzymes. A direct effect of fatty acids on a cis-acting element of the lipogenic enzyme genes could be involved, as the regulatory region of FAS gene contains a polyunsaturated fatty acid response element that shares some similarity with the peroxisome proliferator-activated receptor recently described.
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PMID:Regulation of lipogenic enzyme gene expression by nutrients and hormones. 790 48

Fasting causes a decrease in the rate of synthesis of fatty acid synthase, the central enzyme in fatty acid synthesis, while refeeding carbohydrate increases synthesis. Insulin also increases the synthesis of fatty acid synthase, while glucagon causes a decline. The mechanism was shown to be transcriptional activation-mediated through a 2.1-kb stretch of the 5'-flanking sequence of the fatty acid synthase gene promoter that contains an insulin response element. These effects were confirmed by in vivo experiments with transgenic mice.
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PMID:Nutritional and hormonal regulation of fatty acid synthase. 871 Feb 41


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