UNIPROT:P01275 - FACTA Search

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Query: UNIPROT:P01275 (glucagon)
26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma insulin, glucagon, glucose, free fatty acids and glycerol, hepatic cyclic AMP and glycogen, and liver phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-bisphosphatase (FBPase), glucose 6-phosphatase (G6Pase) and alanine amino transferase (AAT) activities were examined in adult rats during the first 24 h of either starvation or consumption of a high protein, carbohydrate-free (HP) diet. Under both nutritional conditions, plasma insulin fell within 12 h and remained constant thereafter. Glucagon increased 12 h after the start of the experiment and peaked between 18-24 h. The insulin: glucagon ratio was lower during the last 12 h of the experiment. In both experimental groups, liver cyclic AMP increased progressively and peaked between 15-24 h, but it increase was higher on HP diet than on starvation. Whereas plasma glucose remained low on starvation for 24 h, it returned to normal on consumption of the HP diet. In both groups, liver glycogen fell within 12 h and remained low until the end of experiment. FBPase, G6Pase and AAT did not change on starvation, while they increased toward the end of 1 d HP consumption. During starvation or consumption of the HP diet, PEPCK increased progressively and peaked between 15-24 h, but the increase was greater with the HP diet than with starvation. These findings suggest that in the first 24 hours, the adaptative response of hepatic gluconeogenesis is higher with a HP diet than upon starvation.
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PMID:Comparison between starvation and consumption of a high protein diet: plasma insulin and glucagon and hepatic activities of gluconeogenic enzymes during the first 24 hours. 300 46

Acute hormonal regulation of liver carbohydrate metabolism mainly involves changes in the cytosolic levels of cAMP and Ca2+. Epinephrine, acting through beta 2-adrenergic receptors, and glucagon activate adenylate cyclase in the liver plasma membrane through a mechanism involving a guanine nucleotide-binding protein that is stimulatory to the enzyme. The resulting accumulation of cAMP leads to activation of cAMP-dependent protein kinase, which, in turn, phosphorylates many intracellular enzymes involved in the regulation of glycogen metabolism, gluconeogenesis, and glycolysis. These are (1) phosphorylase b kinase, which is activated and, in turn, phosphorylates and activates phosphorylase, the rate-limiting enzyme for glycogen breakdown; (2) glycogen synthase, which is inactivated and is rate-controlling for glycogen synthesis; (3) pyruvate kinase, which is inactivated and is an important regulatory enzyme for glycolysis; and (4) the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase bifunctional enzyme, phosphorylation of which leads to decreased formation of fructose 2,6-P2, which is an activator of 6-phosphofructo-1-kinase and an inhibitor of fructose 1,6-bisphosphatase, both of which are important regulatory enzymes for glycolysis and gluconeogenesis. In addition to rapid effects of glucagon and beta-adrenergic agonists to increase hepatic glucose output by stimulating glycogenolysis and gluconeogenesis and inhibiting glycogen synthesis and glycolysis, these agents produce longer-term stimulatory effects on gluconeogenesis through altered synthesis of certain enzymes of gluconeogenesis/glycolysis and amino acid metabolism. For example, P-enolpyruvate carboxykinase is induced through an effect at the level of transcription mediated by cAMP-dependent protein kinase. Tyrosine amino-transferase, serine dehydratase, tryptophan oxygenase, and glucokinase are also regulated by cAMP, in part at the level of specific messenger RNA synthesis. The sympathetic nervous system and its neurohumoral agonists epinephrine and norepinephrine also rapidly alter hepatic glycogen metabolism and gluconeogenesis acting through alpha 1-adrenergic receptors. The primary response to these agonists is the phosphodiesterase-mediated breakdown of the plasma membrane polyphosphoinositide phosphatidylinositol 4,5-P2 to inositol 1,4,5-P3 and 1,2-diacylglycerol. This involves a guanine nucleotide-binding protein that is different from those involved in the regulation of adenylate cyclase. Inositol 1,4,5-P3 acts as an intracellular messenger for Ca2+ mobilization by releasing Ca2+ from the endoplasmic reticulum.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms of hormonal regulation of hepatic glucose metabolism. 303 41

We studied the effects of insulin and glucagon on energy and carbohydrate metabolism of rat hepatocytes in primary culture. The aim of this study is to elucidate the mechanism of the synergistic action of insulin and glucagon and to evaluate the combined effects of these hormones on liver injury. Insulin increased the level of adenosine triphosphate in hepatocytes in the presence of glucagon. Insulin increased the activities of glucokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40) type L and glucose 6-phosphate dehydrogenase (EC 1.1.1.49). Glucagon had no antagonistic effect on these increases. Glucagon increased the activity of glucose 6-phosphate (EC 3.1.3.9) (G6Pase) in the presence or absence of insulin, while insulin had no effects on the levels of G6Pase and fructose 1,6-bisphosphatase (EC 3.1.3.11) in the presence or absence of glucagon. Metabolite analysis of cultured hepatocytes indicated that insulin and glucagon have antagonistic effects on the glycolytic activity of hepatocytes. These combined effects of insulin and glucagon may partially explain the preventive effects of these hormones on liver injury.
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PMID:Effects of insulin and glucagon on energy and carbohydrate metabolism of rat hepatocytes in primary culture. 306 23

In fetal mouse liver fragments maintained in organ culture, the activities of fructose 1,6-bisphosphatase and glucose 6-phosphatase are elevated in the presence of dibutyryl adenosine 3',5'-monophosphate (Bt2-cAMP). Isobutyl-1-methylxanthine at 2.5 mM increased the two enzyme activities. The enzyme activities returned to the normal levels following removal of Bt2-cAMP from the culture medium. Glucagon at concentrations from 10(-11) M to 10(-6) M induced both enzyme activities. The developmental increases in the two gluconeogenic enzymes are supported by cyclic AMP elevated by glucagon. Only at unphysiologically high concentrations did prostaglandin-E1 show weak stimulatory effects. alpha-Adreno-agonists did not stimulate the enzyme activities. Actinomycin D and cycloheximide reduced the enzyme activities stimulated by Bt2-cAMP. Both inhibitors and removal of Bt2-cAMP prevented the incorporation of [3H]leucine into the bisphosphatase. The kinetic properties, subunit-size, and antigenic nature of the bisphosphate showed that the type of enzyme induced by Bt2-cAMP in vitro is identical to the adult liver type. The results are interpreted as indicating that cyclic AMP acts at certain sites in the syntheses of these two gluconeogenic enzymes in the fetal mouse liver.
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PMID:Induction of fructose 1,6-bisphosphatase and glucose 6-phosphatase by dibutyryl cyclic adenosine monophosphate in fetal mouse liver. 620 65

Three experiments were conducted to assess the effects of magnesium deficiency on the activities of hepatic glucose-6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FDPase) and phosphoenolpyruvate carboxykinase (PEPCK). Experiment 1 was designed to determine if magnesium deficiency interfered with the gluconeogenic response to fasting. Rats were fed either a control (C) or magnesium-deficient (MD) diet for 12 days. One-half of each group of rats was fasted for 24 hours prior to death. Hepatic enzyme activities, plasma and liver magnesium, and whole blood glucose were measured. Activities of G6Pase and PEPCK were higher in fasted group C rats compared to fed group C rats. Activity of FDPase was lower. The response was similar in the MD groups. Comparison of C and MD groups indicated that magnesium deficiency was accompanied by an increase in PEPCK activity. To verify this result and to investigate the role of anorexia in producing increased PEPCK activity, experiment 2 included a pair-fed group (PF). The results indicated that anorexia was not responsible for increased PEPCK activity in MD rats. The relation of circulating insulin and glucagon concentrations to effects of magnesium deficiency was explored in experiment 3. A decreased insulin:glucagon ratio was observed in MD rats. The results of these experiments suggest that magnesium deficiency alters PEPCK activity by affecting secretion of pancreatic hormones.
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PMID:Hepatic gluconeogenic enzymes, plasma insulin and glucagon response to magnesium deficiency and fasting. 627 7

Glucagon and dibutyryl cyclic AMP inhibited glucose utilization and lowered fructose 2,6-bisphosphate levels of hepatocytes prepared from fed chickens. Partially purified preparations of chicken liver 6-phosphofructo-1-kinase and fructose 1,6-bisphosphatase were activated and inhibited by fructose 2,6-bisphosphate, respectively. The sensitivities of these enzymes and the changes observed in fructose 2,6-bisphosphate levels are consistent with an important role for this allosteric effector in hormonal regulation of carbohydrate metabolism in chicken liver. In contrast, oleate inhibition of glucose utilization by chicken hepatocytes occurred without change in fructose, 2,6-bisphosphate levels. Likewise, pyruvate inhibition of lactate gluconeogenesis in chicken hepatocytes cannot be explained by changes in fructose 2,6-bisphosphate levels. Exogenous glucose caused a marked increase in fructose 2,6-bisphosphate content of hepatocytes from fasted but not fed birds. Both glucagon and lactate prevented this glucose effect. Fasted chicken hepatocytes responded to lower glucose concentrations than fasted rat hepatocytes, perhaps reflecting the species difference in hexokinase isozymes.
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PMID:Role of fructose 2,6-bisphosphate in the regulation of glycolysis and gluconeogenesis in chicken liver. 631 91

Isolated rat hepatocytes convert 2,5-anhydromannitol to 2,5-anhydromannitol-1-P and 2,5-anhydromannitol-1,6-P2. Cellular concentrations of the monophosphate and bisphosphate are proportional to the concentration of 2,5-anhydromannitol and are decreased by gluconeogenic substrates but not by glucose. Rat liver phosphofructokinase-1 phosphorylates 2,5-anhydromannitol-1-P; the rate is less than that for fructose-6-P but is stimulated by fructose-2,6-P2. At 1 mM fructose-6-P, bisphosphate compounds activate rat liver phosphofructokinase-1 in the following order of effectiveness: fructose-2,6-P2 much greater than 2,5-anhydromannitol-1,6-P2 greater than fructose-1,6-P2 greater than 2,5-anhydroglucitol-1,6-P2. High concentrations of fructose-1,6-P2 or 2,5-anhydromannitol-1,6-P2 inhibit phosphofructokinase-1. Rat liver fructose 1,6-bisphosphatase is inhibited competitively by 2,5-anhydromannitol-1,6-P2 and noncompetitively by 2,5-anhydroglucitol-1,6-P2. The AMP inhibition of fructose 1,6-bisphosphatase is potentiated by 2,5-anhydroglucitol-1,6-P2 but not by 2,5-anhydromannitol-1,6-P2. Rat liver pyruvate kinase is stimulated by micromolar concentrations of 2,5-anhydromannitol-1,6-P2; the maximal activation is the same as for fructose-1,6-P2. 2,5-Anhydroglucitol-1,6-P2 is a weak activator. 2,5-Anhydromannitol-1-P stimulates pyruvate kinase more effectively than fructose-1-P. Effects of glucagon on pyruvate kinase are not altered by prior treatment of hepatocytes with 2,5-anhydromannitol. Pyruvate kinase from glucagon-treated hepatocytes has the same activity as the control pyruvate kinase at saturating concentrations of 2,5-anhydromannitol-1,6-P2 but has a decreased affinity for 2,5-anhydromannitol-1,6-P2 and is not stimulated by 2,5-anhydromannitol-1-P. The inhibition of gluconeogenesis and enhancement of glycolysis from gluconeogenic precursors in hepatocytes treated with 2,5-anhydromannitol can be explained by an inhibition of fructose 1,6-bisphosphatase, an activation of pyruvate kinase, and an abolition of the influence of phosphorylation on pyruvate kinase.
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PMID:Mechanism of action of 2,5-anhydro-D-mannitol in hepatocytes. Effects of phosphorylated metabolites on enzymes of carbohydrate metabolism. 632 20

2,5-Anhydro-D-mannitol (100 to 200 mg/kg) decreased blood glucose by 17 to 58% in fasting mice, rats, streptozotocin-diabetic mice, and genetically diabetic db/db mice. Serum lactate in rats was elevated 56% by 2,5-anhydro-D-mannitol, but this could be prevented by dichloroacetate (200 mg/kg) or thiamin (200 mg/kg). In hepatocytes from fasted rats, 1 mM 2,5-anhydro-D-mannitol inhibited gluconeogenesis from a mixture of alanine, lactate, and pyruvate. It also inhibited glucose production and stimulated lactate formation from glycerol or dihydroxyacetone. Glycogenolysis in hepatocytes from fed rats was markedly inhibited by 1 mM 2,5-anhydro-D-mannitol both in the presence or absence of 1 microM glucagon. 2,5-Anhydro-D-mannitol can be phosphorylated by fructokinase or hexokinase to the 1-phosphate and then by phosphofructokinase to the 1,6-bisphosphate. Rat liver glycogen phosphorylase was inhibited by 2,5-anhydro-D-mannitol 1-phosphate (apparent Ki = 0.66 +/- 0.09 mM) but was little affected by 2,5-anhydro-D-mannitol 1,6-bisphosphate. Rat liver phosphoglucomutase was inhibited by 2,5-anhydro-D-mannitol 1-phosphate (apparent Ki = 2.8 +/- 0.2 mM), whereas 2,5-anhydro-D-mannitol 1,6-bisphosphate served as an alternative activator (apparent K alpha = 7.0 +/- 0.5 microM). Rabbit liver pyruvate kinase was activated by 2,5-anhydro-D-mannitol 1,6-bisphosphate (apparent K alpha = 9.5 +/- 0.9 microM), whereas rabbit liver fructose 1,6-bisphosphatase was inhibited by 2,5-anhydro-D-mannitol 1,6-bisphosphate (apparent Ki = 3.6 +/- 0.3 microM). The phosphate esters of 2,5-anhydro-D-mannitol would, therefore, be expected to inhibit glycogenolysis and gluconeogenesis and stimulate glycolysis in liver.
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PMID:Inhibition of gluconeogenesis and glycogenolysis by 2,5-anhydro-D-mannitol. 642 25

1. The effects of dietary polychlorinated biphenyls (PCBs) (30-2000 ppm) on activities of gluconeogenic (phosphoenolpyruvate carboxykinase-PEPCK, and fructose 1,6-bisphosphatase-FdPase) and lipogenic enzymes (fatty acid synthase-FAS, ATP citrate lyase-ACL, malic enzyme-ME, glucose 6-phosphate dehydrogenase-G6PDH, and 6-phosphogluconate dehydrogenase-PGDH) were studied in livers of the female Sprague-Dawley and Wistar rat. 2. PCB amounts accumulating in the liver reflected the extent of dietary exposure. The Wistar strain was more sensitive to PCBs than the Sprague-Dawley strain. Of the Clophentype PCBs those containing 60 and 64% chlorine displayed the most pronounced effects. 3. Activities of gluconeogenic enzymes (PEPCK and FdPase) were dose-dependently decreased by PCBs, PEPCK being considerably more sensitive. This decrease was also found under conditions where the activity of PEPCK was induced (administration of adrenalin, glucagon or cAMP, feeding high protein diets, starvation). 4. Activities of lipogenic enzymes were induced by PCBs. The increase was much greater with ME, G6PDH and PGDH (up to 10-fold) than with FAS and ACL (approximately 2-fold). PCB effects were dose-dependent, but transient. 5. In cultured hepatocytes basal activities of lipogenic enzymes were induced by PCBs in the absence of hormones. With saturating levels of insulin or triiodothyronine, enzyme activities were also induced, but addition of PCBs resulted in an additive effect. 6. These results suggest that in the female rat PCBs can mimic the actions of certain hormones by affecting either hormone levels, hormone receptor systems or regulatory systems.
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PMID:Polychlorinated biphenyls affect the activities of gluconeogenic and lipogenic enzymes in rat liver: is there an interference with regulatory hormone actions? 962 50

The levels of glycogen in brain, lactate and acetoacetate in brain and plasma, glucose in plasma and the activities of brain key enzymes of glycogen metabolism (glycogen phosphorylase, GPase, glycogen synthetase, GSase), gluconeogenesis (fructose 1,6-bisphosphatase, FBPase), and glycolysis (6-phosphofructo 1-kinase, PFK) were evaluated in rainbow trout, Oncorhynchus mykiss, from 0.5 to 3 hr after intraperitoneal injection of 1 ml/kg(-1) body weight of saline alone (controls) or containing bovine glucagon at three different doses: 10, 50, and 100 ng/g(-1) body weight. The results obtained demonstrate, for the first time in a teleost fish, the existence of changes in brain carbohydrate and ketone body metabolism following peripheral glucagon treatment. A clear stimulation of brain glycogenolytic potential was observed after glucagon treatment, as judged by the time- and dose-dependent changes observed in brain glycogen levels (up to 88% decrease), and GPase (up to 30% increase) and GSase (up to 42% decrease) activities. In addition, clear time- and dose-dependent increased and decreased levels were observed in brain of glucagon-treated rainbow trout for lactate (up to 60% increase) and acetoacetate (up to 67% decrease), respectively. In contrast, no significant changes were observed after glucagon treatment in those parameters related to glycolytic/gluconeogenic capacity of rainbow trout brain. Altogether, these in vivo results suggest that glucagon may play a role (direct or indirect) in the regulation of carbohydrate and ketone body metabolism in brain of rainbow trout.
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PMID:Glucagon effects on brain carbohydrate and ketone body metabolism of rainbow trout. 1174 15

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