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)

Infant rats were injected with prednisolone (0.5-5 mg/100 g wt). This caused phosphoenolpyruvate carboxykinase (PEPCK) activity to rise in liver and to decrease in brown fat. Fatty acid synthetase (FAS) activity remained unchanged in liver but increased in brown fat. A single injection of prednisolone caused hepatic PEPCK activity to remain elevated for at least 7 days. Brown fat FAS also remained high for that period. However, brown fat PEPK activity returned to normal on the third day after the injection. A single injection of prednisolone or cortisone to 5-day-old rats caused a transient elevation of the blood level of insulin and a prolonged decrease in that of growth hormone. No effect on the level of glucagon was noted. Injections of insulin had effects similar to those of prednisolone, i.e. a rise in hepatic and a fall in brown fat PEPCK. Using antibodies prepared to hepatic PEPCK it was shown that the observed changes were due to changes in the rate of synthesis of the enzyme. Using actinomycin D indirect evidence was obtained that changes in FAS activity of brown fat were also due to changes in the synthetic rate.
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PMID:Regulation of phosphoenolpyruvate carboxykinase and fatty acid synthetase in brown fat of suckling rats. 74 53

Gluconeogenesis by isolated hepatocytes resulted in glucose release but insignificant rates of glycogen synthesis. The effectiveness of precursors was similar for hepatocytes from fed and starved chickens except for impaired gluconeogenesis from pyruvate when compared to lactate in lactate starved chicken hepatocytes. The impairment was caused by limitations in cytosolic NADH production as a result of the mitochondrial location of phosphoenolpyruvate carboxykinase in chicken liver. The order of effectiveness of precursors on hepatic gluconeogenesis was generally similar to the effects of precursors on increasing the plasma glucose concentration in vivo. The exceptions were caused by interactions with other precursors in vivo. The alteration of the NADH/NAD+ ratio by ethanol and ATP/ADP ratio by adenosine could play significant roles in the control of precursor conversion to glucose. Physiological glucagon concentrations stimulated gluconeogenesis from precursors entering the pathway both above and below the level of triose phosphates, and its effect were mimicked by dibutyryl cyclic AMP. Previous results on the effects of precursor and glucagon injection on the plasma glucose concentration of chickens in vivo can largely be explained by effects at the hepatic level. Isolated chicken and rat hepatocytes share many common features. Qualitatively the ordering of gluconeogenic effectiveness was similar but quantitive differences existed as a result of differing activities and cellular locations of enzymes. Neither preparation readily synthesised glycogen and the sensitivity to glucagon was similar.
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PMID:Hepatic gluconeogenesis in chickens. 74 98

To determine the fetal response to altered maternal fuel supply, the effects of prolonged maternal fasting, begun 24-96 h before term, were examined and compared with values from normally fed term animals. Fetal weight decreased only after 48 h of maternal fasting. Prolonged maternal fasting was associated with low blood glucose, high blood ketone bodies, and decreased gluconeogenic substrate in the fetus. Plasma insulin was decreased, whereas plasma glucagon was increased in the fetus of fasted mothers. Infusion of [2-3H]glucose into the mother to constant specific activity gave a ratio of maternal to fetal glucose activity of 1.0 in fed and 1.56 in fasted mothers. Fetal liver from fasted mothers showed both increase in activity of key gluconeogenic enzymes (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) and increased conversion in vitro of lactate, alanine, serine, and glycerol in glucose by liver slices. It is inferred that maternal fasting induces fetal substrate alterations and hormonal changes appropriate to premature appearance of hepatic gluconeogenesis. The priority for endogenous fuel provision in this state leads to impaired fetal growth.
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PMID:Fetal metabolic response to maternal fasting in the rat. 87 Nov 55

Gluconeogenesis was studied in 3 cases of persistent neonatal hypoglycaemia. In 2 of the cases the labelling of blood glucose after i.v. injection of 1415C-alanine was reduced. In these 2 patients only 1.3-5% of the injected radioactivity was recovered in blood glucose, compared with 10% in normoglycaemic patients. The labelling of glucose from 14C-glycerol, as studied in one case, was not reduced. In this patient the labelling of blood glucose from C-alanine was improved after subtotal resection of the pancreas, and with increasing age. By the time of the isotope studies the plasma insulin was normal in all patients, and no deficiency of glucagon secretion could be detected after stimulation with an alanine load. A quantitative amino acid analysis of plasma revealed a moderate increase of some of the glucogenic amino acids. The results were interpreted as a deficiency of gluconeogenesis, probably at the phosphoenolpyruvate carboxykinase or pyruvate carboxylase step.
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PMID:Gluconeogenesis in infancy and childhood. II. Studies on the glucose production from alanine in three cases of persistent neonatal hypoglycaemia. 127 63

The injection of streptozotocin to 18-day-old rat fetuses induced, 2 days later, a 50% fall in plasma insulin and a twofold increase in plasma glucagon concentrations and liver cAMP levels. Phosphoenolpyruvate carboxykinase mRNA that were undetectable in the fetal rat liver, accumulated 48 h after streptozotocin injection, their concentration being 30% of that found in the liver of 1-day-old newborn rats in whom liver phosphoenolpyruvate carboxykinase gene expression is maximal. Physiological concentrations of glucagon (0.7 +/- 0.2 nM) induced, within 2 h, phosphoenolpyruvate carboxykinase mRNA accumulation in cultured hepatocytes from 20-day-old fetuses. The addition of insulin (0.01-100 nM) inhibits, by no more than 30%, the glucagon-induced phosphoenolpyruvate carboxykinase mRNA accumulation. Exposure of fetal hepatocytes to insulin for 24 h did not change the glucagon dose/response curve and did not lead to a more efficient inhibition of the glucagon-induced phosphoenolpyruvate carboxykinase mRNA accumulation, despite a clear stimulatory effect on the rate of lipogenesis. In contrast, when hepatocytes were cultured in the presence of dexamethasone, the glucagon-induced phosphoenolpyruvate carboxykinase mRNA accumulation can be totally inhibited by pharmacological concentrations of insulin (10 nM). From these in-vivo and in-vitro studies, it is concluded that, under physiological conditions, the postnatal rise in plasma glucagon concentration is more important than the fall in the plasma insulin concentration for the primary induction of liver phosphoenolpyruvate carboxykinase gene expression.
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PMID:Dominant role of glucagon in the initial induction of phosphoenolpyruvate carboxykinase mRNA in cultured hepatocytes from fetal rats. 128 85

Fetal hepatocytes cultured for 64 h in the presence of glucagon and dexamethasone maintain a quiescent state, showing a low expression of glucose-6-phosphate dehydrogenase (G6PD) and a high induction of phosphoenolpyruvate carboxykinase (PEPCK). Under these culture conditions, the presence of EGF produced hepatocyte proliferation, with a concomitant increase of DNA synthesis, DNA content, and G6PD expression, meanwhile the expression of PEPCK was drastically reduced. The presence of forskolin plus IBMX nearly suppressed the increase in DNA synthesis and G6PD expression induced by EGF, showing a very high expression of PEPCK. Accordingly, it is possible to establish an inverse relation between G6PD, highly expressed in proliferating fetal hepatocytes, and PEPCK expression, highly expressed in quiescent fetal hepatocytes under specific hormonal stimulation.
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PMID:Phosphoenolpyruvate carboxykinase and glucose-6-phosphate dehydrogenase expression in fetal hepatocyte primary cultures under proliferative conditions. 131 82

Short- and long-term regulation of hepatic carbohydrate metabolism by insulin-like growth factor II was studied in primary cultures of adult rat hepatocytes and compared to the metabolic potency of insulin. Insulin-like growth factor II stimulated glycogen synthesis from [14C]glucose, uptake of [3H]aminoisobutyric acid and [14C]lactate formation from [14C]glucose up to three-fold. Basal glycogenolysis was inhibited to about 10%, and glucagon-activated glycogenolysis was blocked completely. The enzymatic activity of glucokinase and pyruvate kinase was induced two-fold, the glucagon-dependent induction of phosphoenolpyruvate carboxykinase was antagonized. Compared to insulin, half-maximal responses required up to 50 times higher insulin-like growth factor II concentrations ranging from 10-20 nmol/l. A similar difference was observed for binding affinity of insulin-like growth factor II to the insulin receptor. The interaction with the insulin-like growth factor II/mannose 6-phosphate (IGF-II/Man-6-P) receptor was examined by studying 125I-insulin-like growth factor II binding and uptake of lysosomal enzymes. The affinity of insulin-like growth factor II to the IGF-II/Man-6-P receptor was considerably higher than for the insulin receptor. Antibodies against the IGF-II/Man-6-P receptor did not affect metabolic responses to insulin-like growth factor II, while binding to its receptor and the receptor-mediated endocytosis of arylsulphatase A were strongly inhibited. Thus, in adult rat liver insulin-like growth factor II appeared to exert metabolic actions not via interaction with its own receptor but through low affinity binding to hepatic insulin receptors.
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PMID:Metabolic actions of insulin-like growth factor II in cultured adult rat hepatocytes are not mediated through the insulin-like growth factor II receptor. 134 10

The glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK) gene is modulated by oxygen. It was proposed that heme proteins might function as O2 sensors; their actions are impaired after replacement of the central Fe2+ ion by Co2+ and inhibition of heme synthesis by succinylacetone (SA). Therefore, the effects of CoCl2 and SA, alone and in combination, on the glucagon-dependent induction of PCK activity and PCK mRNA were investigated at different physiological oxygen tensions in primary rat hepatocyte cultures. The cells were exposed to 50 microM CoCl2 and/or 2 mM SA from 4-24 h. After addition of fresh media without CoCl2 or SA, PCK was induced with 1 nM glucagon. PCK activity and PCK mRNA were elevated to 100% at 16% O2 and to about 65% at 8% O2. CoCl2 reduced these increases to about 45% at 16% O2 and to about 35% at 8% O2. SA lowered the inductions to about 50% and 40% each at 16% and 8% O2. CoCl2 plus SA diminished the elevations to about 5% at both oxygen tensions. In the presence of CoCl2 and/or SA, ornithine decarboxylase induction by insulin was not impaired; lactate dehydrogenase did not leak from the cells, which in electron microscopical inspections had normal cell structures. These findings support the hypothesis that a heme protein is involved in the activation of the PCK gene and that it acts as an O2 sensor.
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PMID:Modulation of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene by oxygen in rat hepatocyte cultures. Evidence for a heme protein as oxygen sensor. 139 23

2-Oxoglutarate was found to inhibit purified rat liver phosphoenolpyruvate carboxykinase when the assay was performed in the direction of either phosphoenolpyruvate or oxaloacetate synthesis. The inhibition was competitive with respect to oxaloacetate or phosphoenolpyruvate, the Ki values being 0.32 +/- 0.04 mM 0.63 +/- 0.19 mM respectively. 2-Oxoglutarate inhibited non-competitively when tested against GTP or Mn2+. The reported cytosolic concentrations of 2-oxoglutarate in rat hepatocytes are such that the enzyme is likely to be significantly inhibited under basal conditions. The cytosolic concentration of 2-oxoglutarate is known to fall precipitously under the influence of glucagon and other hormones that stimulate gluconeogenesis, and it is suggested that the hormone-induced decrease in 2-oxoglutarate content would alleviate the inhibition of phosphoenolpyruvate carboxykinase and stimulate flux from oxaloacetate to phosphoenolpyruvate. The implications of this finding to the rationalization of the role of pyruvate kinase in the stimulation of gluconeogenesis in the fasted state are discussed.
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PMID:Physiological concentrations of 2-oxoglutarate regulate the activity of phosphoenolpyruvate carboxykinase in liver. 149 14

The relationships between metabolic alterations and tissue-specific gene expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), gamma-interferon (gamma-IFN), and interleukin 1 and serum levels of TNF-alpha and IL-6 before and after a live Escherichia coli septic challenge to rats were examined. From 0 to 2 h, serum glucose significantly decreased while plasma glucagon increased. By 8 h, plasma glucagon, serum insulin, and glucose appearance were significantly elevated. Gene expression of phosphoenolpyruvate carboxykinase increased 1 h after E. coli but by 4 h was significantly decreased. TNF-alpha mRNA (liver and spleen) and serum peptide levels peaked 1-2 h after the septic challenge and then decreased substantially by 6-8 h. Spleen IL-6 and gamma-IFN mRNA expression reached a maximum 4 h after E. coli challenge, whereas serum IL-6 levels were elevated by 2 h after injection of the bacteria. The increase in TNF-alpha mRNA and serum peptide levels correlated with the early fall in serum glucose and rise in plasma glucagon. Alterations in the rate of glucose appearance and plasma glucagon were observed later and coincided with the increased mRNA expression of IL-6 and gamma-IFN. Thus the metabolic alterations observed in the septic rat are associated with a complex cascade of several cytokines.
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PMID:Sepsis-induced cascade of cytokine mRNA expression: correlation with metabolic changes. 159 Mar 83


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