Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

We have recently obtained encouraging short-term results after a single subcutaneous injection of the long-acting somatostatin analogue SMS 201-995 in acromegalic patients. Increased growth hormone (GH) levels may be involved in the pathogenesis of proliferative retinopathy in type I diabetes mellitus. In this study we thus investigated the effect of 3 X 50 micrograms SMS 201-995 daily on the metabolic control and hormone secretion of eight type I diabetics over a 3-day period. GH levels decreased by 32% (p less than 0.05) and somatomedin C levels by 31% (p less than 0.01) on the 3rd day of treatment compared with a control day. The insulin requirements during conventional subcutaneous insulin therapy were reduced by 28% (p less than 0.01) in seven patients without deterioration of metabolic control (mean blood glucose levels, 153.8) versus 154.7 mg/dl). Triiodothyronine, thyroxine, glucagon, prolactin, luteinizing hormone and follicle-stimulating hormone showed no significant changes. We conclude that SMS 201-995 could be an excellent tool for further clinical investigation and therapy of diabetic vascular complications.
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PMID:Somatostatin analogue SMS 201-995 in type I diabetes mellitus. Initial experience after repeated administration. 287 2

Recently we reported that hyperglucagonemia induced by glucagon infusion causes a decline in serum Triiodothyronine (T3) and a rise in reverse T3 (rT3) in euthyroid healthy volunteers. These changes in T3 and rT3 levels were attributed to altered T4 metabolism in peripheral tissues. However, the contribution of altered release of thyroid hormones by the thyroid gland could not be excluded. Since the release of thyroid hormones is suppressed by exogenous administration of L-thyroxine (L-T4) in appropriate dosage, we studied thyroid hormone levels for up to 6 hours after intravenous administration of glucagon in euthyroid healthy subjects after administration of L-T4 for 12 weeks. A control study was conducted using normal saline infusion. Plasma glucose rose promptly following glucagon administration demonstrating its physiologic effect. Serum T4, Free T4 and T3 resin uptake were not altered during both studies. Glucagon infusion induced a significant decline in serum T3 (P less than 0.01) and a marked rise in rT3 (P less than 0.01) whereas saline administration caused no alterations in T3 or rT3 levels. Thus the changes in T3 and rT3 were significantly different during glucagon study when compared to saline infusion. (P less than 0.01 for both comparisons). Therefore, this study demonstrates that changes in serum T3 and rT3 caused by hyperglucagonemia may be secondary to altered thyroid hormone metabolism in peripheral tissues and not due to altered release by the thyroid gland, since the release of thyroid hormones is suppressed by exogenous L-T4 administration.
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PMID:Decline of T3 and elevation in reverse T3 induced by hyperglucagonemia: changes in thyroid hormone metabolism, not altered release of thyroid hormones. 318 70

Mechanisms involved in stimulation of the synthesis of malic enzyme by insulin and triiodothyronine and in inhibition of synthesis by glucagon have been investigated by assessing levels and rates of synthesis of malic enzyme mRNA in chick embryo hepatocytes in culture. Insulin alone had no effect on the level of malic enzyme mRNA, whereas triiodothyronine by itself caused a 7-fold increase. Insulin plus triiodothyronine caused an 11-fold increase. Glucagon caused a 93% decrease in the accumulation of malic enzyme mRNA caused by insulin plus triiodothyronine. Although the relative changes in mRNA level are smaller in magnitude, they are qualitatively similar to the effects of these hormones on synthesis of malic enzyme, suggesting that control is exerted primarily at pretranslational steps. After addition of triiodothyronine, malic enzyme mRNA accumulated with sigmoidal kinetics, approaching a new steady state at 36-48 h after adding hormone. Puromycin, an inhibitor of protein synthesis, blocked the effect of triiodothyronine if added 30 min prior to the hormone and inhibited further accumulation of malic enzyme mRNA if added 24 h after triiodothyronine. However, puromycin had no effect on the level of beta-tubulin mRNA (t1/2 = 3-5 h), suggesting that the effect of triiodothyronine on malic enzyme mRNA required synthesis of a peptide. Triiodothyronine increased transcription of the malic enzyme gene by 2-fold and level of its mRNA by 11-14-fold, indicating regulation is primarily at a post-transcriptional step. Glucagon caused malic enzyme mRNA to decay with a half-life of 1.5 h, whereas alpha-amanitin or actinomycin D, inhibitors of transcription, caused the mRNA to decay with a half-life of 8-11 h. The effect of glucagon was entirely post-transcriptional because the hormone had no effect on transcription. Taken together, these results suggest a model in which triiodothyronine regulates production of a peptide that stabilizes malic enzyme transcripts in the cytoplasm and/or nucleus. Glucagon may inhibit activity of the peptide induced by triiodothyronine.
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PMID:Hormonal regulation of lipogenic enzymes in chick embryo hepatocytes in culture. Thyroid hormone and glucagon regulate malic enzyme mRNA level at post-transcriptional steps. 352 58

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

Monolayer cultures were prepared from hepatocytes of 15 d chick embryos and maintained at high cell density in a chemically defined medium. In the absence of growth stimulatory conditions DNA synthesis was observed only during the first 10 to 16 h of culture. Thus, after a 12 h exposure to [3H]thymidine ([3H]dThd, 4 to 16 h) 9.1 +/- 1% (mean +/- SD, n = 4) of the hepatocyte nuclei were labeled. Labeled mitotic nuclei, up to late telophase, were regularly observed in these cultures. Beyond 16 h less than 2% labeled nuclei were found (12 h of [3H]dThd), which indicates that the hepatocytes entered proliferative quiescence. DNA synthesis of "resting" hepatocytes was stimulated by insulin and, only slightly, by hydrocortisone, glucagon, or fetal bovine serum. Triiodothyronine (T3), or the nucleoside inosine (i) did not stimulate. Combination of insulin (I) with hydrocortisone (H), T3 (T), or glucagon (G) resulted in a more than additive effect. Nearly maximal stimulation occurred with the combinations IHT and ITG. Labeling increased at 10 ng/ml of each component and was maximal at 1 to 10 micrograms/ml. A lag period of 8 to 10 h after hormone administration (IHiTG, 10 micrograms/ml) was observed before nuclear labeling increased. Within the subsequent 10 h a considerable proportion of the hepatocytes (up to 30% or more) entered DNA synthesis. Mitotic activity (with nuclei in prophase up to late telophase) also was stimulated. An increase of both total DNA and protein content was measured in several experiments. Hormonal stimulation of hepatocyte DNA synthesis and mitotic activity was associated with decreased beta-naphthoflavone-mediated induction of cytochrome P450. A causal relationship between these two phenomena remains to be established. It is suggested that chick embryo hepatocyte cultures are a useful tool for studies on hepatocyte proliferation and differentiation.
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PMID:Stimulation of DNA synthesis and mitotic activity of chick embryo hepatocytes in primary culture. Effect on induction of polysubstrate monooxygenase activity. 637 Aug 35

Triiodothyronine (T3) production from thyroxine (T4) was studied in isolated rat hepatocytes. With an initial T4 concentration of 0.56 microM, hepatocyte T3 production was 0.029 +/- 0.003 (SEM) pmoles/min/mg protein. T3 production was greater in hepatocytes than in homogenates from the same liver prepared either before or after liver perfusion with collagenase. Most T3 produced remained within the cells under the conditions employed. Hepatocyte T3 production was dependent on cell number, medium bovine serum albumin concentration and temperature. It was stimulated by dithiothreitol, and inhibited by propylthiouracil, 3,3',5'-triiodothyronine and dinitrophenol; glutathione and ouabain had no effect. Alterations in medium glucose concentration and exposure to insulin or glucagon at several glucose concentrations in vitro did not alter T3 production. These results indicate that in hepatic tissue T3 production is enhanced when intact cellular organization is present and that insulin and glucagon do not acutely influence cell production of T3 in vitro.
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PMID:Triiodothyronine production by isolated rat hepatocytes: characterization and lack of glucoregulatory hormone effects. 639 64

1. The effect of triiodothyronine on the metabolism of palmitate, oleate and erucate in isolated rat hepatocytes was studied. 2. In triiodothyronine-treated rats increased oxidation and decreased triacylglycerol formation from palmitate and oleate was observed. For erucate triiodothyronine caused increased oxidation, but had no significant effect on esterification. 3. Glucagon had no effect on the fatty acid metabolism in hepatocytes from triiodothyronine-treated rats, whereas it stimulated the oxidation in hepatocytes from normal rats. Still, after treatment with triiodothyronine, the oxidation of fatty acids was significantly higher than in glucagon-stimulated normal hepatocytes. 4. In isolated rat liver mitochondria triiodothyronine raised the activity of the outer carnitine palmitoyltransferase (EC 2.3.1.21). The activity of the total carnitine palmitoyltransferase was elevated only slightly in isolated mitochondria from triiodothyronine-treated rats. These effects were similar to those seen in fasted rats. 5. Triiodothyronine had no significant influence on the concentration of long-chain acyl-CoA or alpha-glycerophosphate in isolated rat hepatocytes.
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PMID:The metabolism of fatty acids in hepatocytes isolated from triiodothyronine-treated rats. 706 76

In cultured adipose tissue of suckling rats, glucose alone is able to induce the appearance of fatty-acid synthase and acetyl-CoA carboxylase mRNA by a mechanism involving glucose-6-phosphate accumulation; insulin alone has no effect but potentiates the effect of glucose. In the present study, we have analysed in cultured adipose tissue the effects of other hormones on the expression of these enzymes as well as on phosphoenolpyruvate carboxykinase. Triiodothyronine has only a marginal effect on fatty-acid synthase expression, in the absence or presence of glucose and insulin. A synthetic glucocorticoid, dexamethasone, opposes the inductive effect of glucose and insulin on fatty-acid synthase expression but increases the expression of phosphoenolpyruvate carboxykinase. A beta-agonist, isoproterenol totally inhibits the inductive effect of glucose and insulin on acetyl-CoA carboxylase and fatty-acid synthase expression whereas it increases the expression of phosphoenolpyruvate carboxykinase. Similarly, glucagon and cAMP have antagonistic effects on glucose and insulin-induced fatty-acid synthase expression. These inhibitory effects cannot be explained only by a reduction in glucose-6-phosphate concentration. We conclude that, in adipose tissue, dexamethasone and cAMP-generating hormones are negative regulators of lipogenic enzyme expression. Finally, the regulation of phosphoenolpyruvate carboxykinase expression in adipose tissue is similar to that found in the liver, i.e. inhibition by insulin and glucose and activation by glucocorticoids and cAMP.
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PMID:Regulation of lipogenic enzyme and phosphoenolpyruvate carboxykinase gene expression in cultured white adipose tissue. Glucose and insulin effects are antagonized by cAMP. 791 89

Four Dorset wethers were studied in a Latin square design with 72-h periods to determine the metabolic adaptations that occur in support of increased glucose demand in ruminants. Wethers injected at 8-h intervals with excipient or a total of .5, 1.0, or 2.0 g/d of phlorizin excreted an average of 0, 72.7, 97.9, and 98.5 g/d of glucose into the urine, respectively. Both acute (2 to 24 h after the first injection) and chronic (8-h intervals from 8 to 72 h after the first injection) adaptations of plasma variables to phlorizin treatment were assessed. Concentrations of plasma glucose decreased linearly with increasing phlorizin dose during the 1st 24 h of treatment and tended to decrease linearly with phlorizin dose during 8 to 72 h of treatment. Urea N tended to increase linearly during 2 to 24 h and increased linearly during 8 to 72 h. Nonesterified fatty acids increased linearly with phlorizin injection during the entire treatment period. beta-Hydroxybutyrate increased quadratically with phlorizin injection during 2 to 24 h and tended to increase quadratically during 8 to 72 h. The ratio of insulin to glucagon tended to decrease linearly with phlorizin injection during the 1st 24 h but was unaffected from 8 to 72 h. Triiodothyronine, but not thyroxine, tended to decrease linearly with phlorizin injection during 8 to 72 h. Cortisol was not affected by treatment. Digestibilities of energy and N were not affected by treatment. Urinary energy excretion increased with phlorizin injection in proportion to the amounts of glucose excreted into the urine. These data indicate that phlorizin-treated wethers largely adapted to phlorizin treatment by 24 h after the first injection and are a suitable model for further investigations of hepatic adaptation to increased glucose demand in ruminants.
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PMID:Metabolic adaptation to experimentally increased glucose demand in ruminants. 985 5


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