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)

Birth in most mammalian species represents an abrupt change from a high-carbohydrate and low-fat diet to a high-fat and low-carbohydrate diet. Gluconeogenesis is absent from the liver of the fetus of well-fed mothers, but can be induced prematurely by prolonged fasting of the mother. Gluconeogenesis increases rapidly in the liver of newborn mammals in parallel with the appearance of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of this pathway. The rise in plasma glucagon and the fall in plasma insulin which occur immediately after birth are the main determinants of liver PEPCK induction. When liver PEPCK has reached its adult value, i.e. 24 h after birth, other factors are involved in the regulation of hepatic gluconeogenesis. In order to maintain a high gluconeogenic rate, the newborn liver must be supplied with sufficient amount of gluconeogenic substrates and free fatty acids. An active hepatic fatty acid oxidation is necessary to support hepatic gluconeogenesis by providing essential cofactors such as acetyl CoA and NADH. The relevance of animal studies for the understanding of neonatal glucose homeostasis in man is discussed.
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PMID:[Hormonal control of the development of hepatic gluconeogenesis in the neonate]. 305 68

Birth in most mammalian species represents an abrupt change from a high-carbohydrate and low-fat diet to a high-fat and low-carbohydrate diet. Gluconeogenesis is absent from the liver of the fetus of well fed mothers, but can be induced prematurely by prolonged fasting of the mother. Gluconeogenesis increases rapidly in the liver of newborn mammals in parallel with the appearance of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of this pathway. The rise in plasma glucagon and the fall in plasma insulin which occur immediately after birth are the main determinants of liver PEPCK induction. When liver PEPCK has reached its adult value, i.e. 24 h after birth, other factors are involved in the regulation of hepatic gluconeogensis. In order to maintain a high gluconeogenic rate, the newborn liver must be supplied with sufficient amount of gluconeogenic substrates and free fatty acids. An active hepatic fatty acid oxidation is necessary to support hepatic gluconeogenesis by providing essential cofactors such as acetyl CoA and NADH. The relevance of animal studies for the understanding of neonatal glucose homeostasis in man is discussed.
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PMID:Gluconeogenesis in late fetal and early neonatal life. 354 66

Incubation of rat adipocytes with the same range of noradrenaline concentrations that stimulate lipolysis caused a rapid and stable decrease in the activity of fatty acyl-CoA synthetase. Corticotropin, glucagon and dibutyryl cyclic AMP also decreased the activity of the enzyme. The effect of noradrenaline was apparent over a wide range of concentrations for the three substrates of the enzyme. A novel fluorescence assay of fatty acyl-CoA synthetase using (1,N6-etheno)-CoA is described. The effect of noradrenaline was not abolished by inclusion of albumin in homogenization buffers, persisted through subcellular fractionation and isolation of microsomes (microsomal fractions) and even survived treatment of microsomes with Triton X-100. The effect of noradrenaline was rapidly reversed within cells by the subsequent addition of insulin or propranolol. The inclusion of fluoride in homogenization buffers did not alter the observed effect of noradrenaline. Additions of cyclic AMP-dependent protein kinase to adipocyte microsomes caused considerable phosphorylation of microsomal protein by [gamma-32P]ATP, but did not affect the activity of fatty acyl-CoA synthetase.
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PMID:Reversible inactivation by noradrenaline of long-chain fatty acyl-CoA synthetase in rat adipocytes. 388 97

The effect of glucagon and insulin on the incorporation of 1-14C-acetate into cholesterol and fatty acids and on the enzymes involved in the first steps of cholesterol synthesis (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, 3-hydroxy-3-methyl-glutaryl-coenzyme A synthase, and acetoacetyl-coenzyme A thiolase) was investigated. Isolated rat hepatocytes at different stages of fetal and postnatal development were employed. Data obtained show the appearance of hormonal control on the 18th day of fetal life, indicating the same pattern, as regards acetate incorporation and HMGCoA reductase prepared and assayed in the presence of NaF. On the contrary, HMGCoA reductase, prepared without NaF, HMGCoA synthase, and acetoacetyl CoA thiolase, does not appear to respond to hormonal stimulation. In the perinatal period, the hormonal effect is no longer detectable, probably because of a hormone resistance of this metabolic pathway.
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PMID:Hormonal control of cholesterogenesis and related enzymes in isolated rat hepatocytes during pre- and postnatal development. 390 31

The effect of 20 L-amino acids upon pancreatic glucagon secretion has been studied in conscious dogs. Each amino acid was administered intravenously over a 15 min period in a dose of 1 mmole/kg of body weight to a group of four or five dogs. Pancreatic glucagon and insulin were measured by radioimmunoassay. 17 of the 20 amino acids caused a substantial increase in plasma glucagon. Asparagine had the most glucagon-stimulating activity (GSA), followed by glycine, phenylalanine, serine, aspartate, cysteine, tryptophan, alanine, glutamate, threonine, glutamine, arginine, ornithine, proline, methionine, lysine, and histidine. Only valine, leucine, and isoleucine failed to stimulate glucagon secretion, and isoleucine may have reduced it. No relationship between glucagon-stimulating activity and insulin-stimulating activity was observed. The amino acids which enter the gluconeogenic pathway as pyruvate and, which are believed to provide most of the amino acid-derived glucose, had a significantly greater GSA than the amino acids which enter as succinyl CoA or as alpha-ketoglutarate. However, pyruvate itself did not stimulate glucagon secretion. The R-chain structure of the amino acid did not appear to be related to its GSA, except that the aliphatic branched chain amino acids, valine, leucine, and isoleucine, were devoid of GSA.
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PMID:Glucagon-stimulating activity of 20 amino acids in dogs. 463 19

Glucagon is able to diminish the net release of inorganic phosphate (Pi) occurring on incubation of isolated hepatocytes from 48-h-starved rats. Concomitantly the hormone increases the cellular Pi content. This is associated with a rise of Pi in the cytosolic fraction. Other hormonal effectors like phenylephrine, vasopressin and angiotensin II exert a smaller and transient effect as compared to glucagon. It is proposed that this increase in Pi availability to the mitochondria, by favouring substrate level phosphorylation at the succinyl-CoA synthetase step plays a role in the development of the metabolite pattern found in the mitochondrial matrix space after exposure of hepatocytes to glucagon or the above agents. With regard to the glutamate level this view is evidenced by the finding that its hormone-dependent decrease was inversely correlated to the respective increase in the cytosolic Pi concentration. Further evidence is provided by experiments with isolated mitochondria incubated under state-3 conditions at medium Pi concentrations corresponding to those metabolically active in the cytosolic compartment of control and glucagon-stimulated hepatocytes, being 2 mM and 3 mM, respectively. Increasing medium phosphate concentration from 2 mM to 3 mM caused a marked decrease in the level of succinyl-CoA and increased the rates of 2-oxoglutarate utilization and of malate and phosphoenolpyruvate production. Citrulline synthesis also was found to be stimulated at 3 mM Pi. Taken together our results suggest a role of Pi supply in mitochondrial actions of glucagon in intact hepatocytes. Moreover, they could contribute to a better interpretation of glucagon effects on isolated mitochondria from hormone-pretreated liver cells.
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PMID:Possible role of Pi supply in mitochondrial actions of glucagon. 614 21

Ketogenesis may be controlled at several sites. Lipolysis with release of plasma nonesterified fatty acid (NEFA) substrate is the first step. Plasma NEFA are taken up by the liver in a concentration-dependent fashion and, after conversion to the acyl-CoA derivative, may either be reesterified or enter the mitochondria via the carnitine shuttle. After beta-oxidation the resultant acetyl-CoA may either be converted to ketone bodies that are then released into the circulation or be condensed with oxaloacetate and enter the tricarboxylic acid cycle, the third potential control point. In humans, infusion of epinephrine causes a transient two- to threefold increase in fatty acids, glycerol, and ketone bodies. Insulin levels show a small absolute increase. Norepinephrine has similar effects, although insulin levels tend to be suppressed and glucagon levels rise somewhat. If somatostatin is added simultaneously, the lipolytic and ketogenic effects are accentuated and prolonged. Dopamine, in a high dose, has no effect on ketone bodies alone but shows small increases in NEFA and ketone bodies in the presence of somatostatin and may play a modulatory role in ketogenesis. The ketogenic effect of catecholamines could thus be in the adipocyte or in the liver. Studies with perfused liver or hepatocytes showed only trivial effects on ketogenesis even with supraphysiological doses of catecholamines. Furthermore infusion studies in rats showed decreased rather than increased ketogenesis with no change in NEFA levels. The data suggest that a) there are species differences, and b) in humans epinephrine- and norepinephrine-induced increases in ketogenesis are secondary to increases in NEFA substrate supply.
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PMID:Mechanisms of catecholamine effects on ketogenesis. 614 93

Male rats underwent either portacaval shunt or portacaval transposition; in both cases, sham-operated pair-fed rats served as controls. Three weeks after a portacaval shunt, fasting serum values of glucose (-35%) and cholesterol (-24%) were lower, and fasting plasma glucagon was higher (+65%). The wet weight of the liver and its total content in DNA, RNA, and protein decreased by 43, 40, 43, and 48%, respectively. The supernatant of liver obtained after centrifugation at 700 g incorporated less [1-14C]acetate (-56%) into fatty acids and less [1-14C]acetate (-94%) and [2-14C]mevalonate (-37%) into cholesterol. The activity of acetyl CoA carboxylase was reduced by 56%. The in vivo incorporation of [3H]H2O into liver fatty acids was 83% lower and that into liver cholesterol was 39% lower than in pair-fed controls. Several of the preceding parameters, including in vitro and in vivo labeling of hepatic fatty acids and cholesterol, were found to be mostly normal in rats with portacaval transposition. These data suggest that the reduction of fatty acid and cholesterol biosynthesis in the liver of rats with portacaval shunt was due to the reduction of total hepatic blood flow rather than to the diversion of portal blood constituents.
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PMID:Effects of portacaval shunt and transposition on fatty acid and cholesterol biosynthesis in rat liver. 615 28

We studied the effects of glucagon, dibutyryl cyclic AMP and dexamethasone on the rate of [(14)C]pantothenate conversion to CoA in adult rat liver parenchymal cells in primary culture. The presence of 30nm-glucagon increased the rate by about 1.5-fold relative to control cultures (range 1.4-2.3) and 2.4-fold relative to cultures containing 1-3m-i.u. of insulin/ml. The half-maximal effect was obtained at 3nm-glucagon. Dibutyryl cyclic AMP plus theophylline also enhanced the rate by about 1.5-fold. Dexamethasone acted synergistically with glucagon; glucagon at 0.3nm had no effect when added alone, but resulted in a 1.7-fold enhancement when added in the presence of dexamethasone (maximum effect at 50nm). The 1.4-fold enhancement caused by the addition of saturating glucagon concentrations was increased to a 3-fold overall enhancement by the addition of dexamethasone. However, dexamethasone added alone over the range 5nm to 5mum had no effect on the rate of [(14)C]pantothenate conversion to CoA. The stimulatory effect of dibutyryl cyclic AMP plus theophylline was also enhanced by the addition of dexamethasone. Changes in intracellular pantothenate concentration or radioactivity could not account for the stimulatory effects of glucagon, dibutyryl cyclic AMP or dexamethasone. Addition of 18mum-cycloheximide, an inhibitor of protein synthesis, decreased the rate of incorporation of [(14)C]pantothenate into CoA and the enhancement of this rate by glucagon and dibutyryl cyclic AMP plus theophylline in a reversible manner. These results demonstrate an influence of glucagon, dibutyryl cyclic AMP and glucocorticoids on the intracellular mechanism regulating total CoA concentrations in the liver.
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PMID:Regulation of coenzyme A biosynthesis by glucagon and glucocorticoid in adult rat liver parenchymal cells. 625 May 39

The effect of different thyroid states on the oxidation of free fatty acids was investigated in the isolated perfused liver of 24-h-starved rats. 1. Compared with the euthyroid control the oxidation of oleate to ketone bodies as well as to CO2 was increased in hyper-, while it was unchanged in hypothyroid livers. 2. The addition of carnitine stimulated oleate oxidation in livers from eu- and hyperthyroid rats, but was without effect in hypothyroid livers. 3. Glucose did not affect the thyroid hormone-mediated effect of oleate conversion to ketone bodies. 4. Hepatic oxidation of octanoate was similar in all thyroid states. 5. Re-esterification of oleate was enhanced in hypo-, but reduced in hyperthyroidism. 6. The concentration of hepatic malonyl-CoA was decreased in hypo- and unchanged in hyperthyroid livers. 7. The concentration of cyclic AMP was elevated in the liver of hyperthyroid rats, no differences were observed between eu- and hypothyroid livers. However, increasing the hepatic cyclic AMP content by the addition of glucagon did not stimulate ketogenesis in eu- and hypothyroid livers. 8. The results indicate that thyroid hormones stimulate oleate oxidation by an accelerated transport of its CoA derivative into the mitochondrial compartment.
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PMID:Effect of thyroid state on ketogenic capacity of the isolated perfused liver of starved rats. 627 88


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