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

The rapid isolation of high yields of parenchymal cells from chicken liver is described. Stringent tests of viability show that the isolated hepatocytes are both structurally and metabolically similar to those in intact liver. During incubation viability decreased and the significance of this change on the interpretation of metabolic experiments is discussed. Lactate was a much more effective gluconeogenic precursor than pyruvate even in the presence of additional reducing equivalents. Hepatocytes isolated from fed chickens produced glucose from glycogen degradation. Glycogenolysis was stimulated by glucagon, dibutyryl cyclic AMP and adrenaline. Half maximal glucagon effects were elicited by physiological concentrations of the hormone. Glucagon and dibutyryl cyclic AMP stimulated glucagon, dibutyryl cyclic AMP and adrenaline their action was not additive to that of adrenaline.
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PMID:The use of viable hepatocytes to study the hormonal control of glycogenolysis in the chicken. 20 19

Glucagon and N,(6)O(2)-dibutyryl cyclic adenosine 3',5'-cyclic monophosphate (Bt(2)cAMP) inhibit fatty acid synthesis from acetate by more than 90% and prevent citrate formation in chick hepatocytes metabolizing glucose. With substrates that enter glycolysis at or below triose-phosphates, e.g., fructose, lactate, or pyruvate, Bt(2)cAMP has no effect on the citrate level and its inhibitory effect on fatty acid synthesis is substantially reversed. Because acetyl-CoA carboxylase requires a tricarboxylic acid activator for activity, it is proposed that regulation of fatty acid synthesis by Bt(2)cAMP is due, in part, to changes in the citrate level. Reduced citrate formation appears to result from a cAMP-induced inhibition of glycolysis. Bt(2)cAMP inhibits (14)CO(2) production from [1-(14)C]-, [6-(14)C]-, and [U-(14)C]glucose and has little effect on (14)CO(2) formation from [1-(14)C]- or [2-(14)C]pyruvate or from [1-(14)C]fructose. [(14)C]Lactate formation from glucose is depressed 50% by Bt(2)cAMP. In the presence of an inhibitor of mitochondrial pyruvate transport lactate accumulation is enhanced, but continues to be lowered 50% by Bt(2)cAMP. The activity of phosphofructokinase is greatly decreased in Bt(2)cAMP-treated cells while the activities of pyruvate kinase and acetyl-CoA carboxylase are unaffected. It appears that decreased glycolytic flux and decreased citrate formation result from depressed phosphofructokinase activity. Fatty acid synthesis from [(14)C]acetate is partially inhibited by Bt(2)cAMP in the presence of fructose, lactate, and pyruvate despite a high citrate level. Incorporation of [(14)C]fructose, [(14)C]pyruvate, or [(14)C]lactate into fatty acids is similarly depressed by Bt(2)cAMP. Synthesis of cholesterol from [(14)C]acetate or [2-(14)C]pyruvate is unaffected by Bt(2)cAMP. These results implicate a second site of inhibition of fatty acid synthesis by Bt(2)cAMP that involves the utilization, but not the production, of cytoplasmic acetyl-CoA.-Clarke, S. D., P. A. Watkins, and M. D. Lane. Acute control of fatty acid synthesis by cyclic AMP in the chick liver cell: possible site of inhibition of citrate formation.
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PMID:Acute control of fatty acid synthesis by cyclic AMP in the chick liver cell: possible site of inhibition of citrate formation. 23 Feb 68

1. The hormonal control of glycogen breakdown was studied in hepatocytes isolated from livers of fed rats. 2. Glucose release was stimulated by [8-arginine]vasopressin (10pm-10nm), oxytocin (1nm-1mum), and angiotensin II (1nm-0.1mum). These responses are all at least as sensitive to hormone as is glucose output in the perfused rat liver. 3. The effect of these three hormones on glucose release was critically dependent on extracellular Ca(2+), unlike that of glucagon. Half-maximal restoration of the vasopressin response occurred if 0.3mm-Ca(2+) was added back to the incubation medium. 4. Glycogen breakdown was more than sufficient to account for the glucose released into the medium, in the absence or presence of hormones. Lactate release by hepatocytes was not affected by vasopressin, but was inhibited by glucagon. 5. If Ca(2+) was omitted from the extracellular medium, vasopressin stimulated glycogenolysis, but not glucose release. 6. The phosphorylase a content of hepatocytes was increased by vasopressin, oxytocin and angiotensin II; minimum effective concentrations were 0.1pm, 0.1nm and 10pm respectively. This response was also dependent on Ca(2+). 7. These results demonstrate that hepatocytes can respond to low concentrations of vasopressin and angiotensin II, i.e. these effects are likely to be relevant in the intact animal. The role of extracellular Ca(2+) in the effects of these hormones on hepatic glycogenolysis and glucose release is discussed.
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PMID:Rapid stimulation by vasopressin, oxytocin and angiotensin II of glycogen degradation in hepatocyte suspensions. 66 48

Hepatocytes were isolated from fed rats with glucose and insulin and freom fasted rats with glucagon in all media in an attempt to obtain cells which might be fixed preferentially in either the glycolytic or gluconeogenic state. When tested enzymatically, both "fed" and fasted" cells catalyzed glucose formation from lactate (gluconeogenesis) and lactate formation from fructose (fructolysis); lactate formation from glucose may have occurred in "fed" cells. Thus it was impossible, at least in the C3 part of the metabolic pathways between triosephosphate and pyruvate, to fix the hepatocytes in either metabolic state. The shift from glycolysis to gluconeogenesis could be investigated for the C3 part in "fasted" cells with fructose as the glycolytic and lactate as the gluconeogenic substrate. Lactate was first formed from fructose and later reutilized to a large extent. This reconsumption was blocked by the gluconeogenesis inhibitor quinolinate, both when tested enzymatically and radiochemically. Thus fructolysis was shifted to lactate gluconeogenesis. This shift at the assumed phosphoenolpyruvate/pyruvate cycle was autoregulatory, i.e. dependent on substrates and independent of circulating horomes. Maximal velocities and half saturating concentrations were determined for fructose and for lactate as substrates. The kinetic data obtained, especially the sigmoidal pattern of fructolysis, could nicely explain phenomenologically the rather sudden slow-down of lactate production and the shift to lactate consumption. The levels of the metabolites ATP, ADP, AMP, fructose bisphosphate and alanine, which control the enzymes of the assumed phosphoenolypyruvate/pyruvate cycle, were determined in the cytosol and in the mitochondria before and after the shift from fructose glycolysis to lactate gluconeogenesis. The changes observed could not explain the shift. Experiments with [14C] fructose plus unlabelled lactate and reciprocally, with unlabelled fructose plus [14C] lactate, clearly reveled that within the C3 part, glycolysis and gluconeogenesis were catalyzed simultaneously. The simultaneity of and the shift between fructolysis and gluconeogenesis by the liver cell suspension can best be explained by assuming two metabolically different types of hepatocytes rather than one type of hepatocyte with metabolically equal or different cell compartment. In vivo, the different types of hepatocytes would form a gluconeogenic and a glycolytic zone within the liver parenchyma. Since, under normal conditions, the size of these metabolic zones should remain unaltered, the shift from net glycolysis to net gluconeogenesis would be dependent primarily on substrate concentrations (autoregulation).
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PMID:Autoregulatory shift from fructolysis to lactate gluconeogenisis in rat hepatocyte suspensions. The problem of metabolic zonation of liver parenchyma. 95 64

Hepatocyte-hepatoma hybrid cells were obtained by fusion of hepatocytes from adult rats and Fao hepatoma cells in the presence of polyethylene glycol. These hybrids were called hepatocytoma cells. The preservation of liver-specific enzyme activities and metabolic functions was studied in the hybrid clone 1E3. 1) The proliferating hepatocytoma cells formed monolayers presenting morphological similarity to primary cultures of hepatocytes. 2) In contrast to Fao hepatoma cells, activities of all gluconeogenic key enzymes were preserved at normal or reduced levels. 3) Lactate-dependent glucose formation was maintained at a state reduced to 36% of the gluconeogenesis in hepatocytes; no glucose formation was detected in Fao hepatoma cells. 4) The activity of the liver-specific glucokinase was reduced in hepatocytoma cells, but it was still present in contrast to Fao cells. The liver-specific isoenzyme pyruvate kinase type L was replaced by the isoenzyme type M2. 5) Gluconeogenic and glycolytic enzyme activities were regulated in hepatocytoma cells by glucagon (0.1 microM) and by insulin (0.1 microM). 6) The genome of hepatocytoma cells and its expression were stable for at least one year, when spontaneously dedifferentiating cells were removed by recloning in hypoxanthine-aminopterine-thymidine (HAT) medium.
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PMID:Hormone-sensitive carbohydrate metabolism in rat hepatocyte-hepatoma hybrid cells. 132 97

The effects of ingesting a low dose of CHO on plasma glucose, glucoregulatory hormone responses, and performance during prolonged cycling were investigated. Nine male subjects cycled for 165 min at approximately 67% peak VO2 followed by a two-stage performance ride to exhaustion on two occasions in the laboratory. Every 20 min during exercise, subjects consumed either a flavored water placebo (P) or a dilute carbohydrate beverage (C). Blood samples were collected immediately before, every 20 min throughout, and immediately after exercise. Plasma was analyzed for glucose, lactate, free fatty acids (FFA), and various glucoregulatory hormones. VO2, RER, heart rate, perceived exertion, and exercise performance were also measured. Lactate, FFA, epinephrine, norepinephrine, ACTH, cortisol, and glucagon increased with exercise whereas glucose and insulin decreased (p < or = .05). Except for a small difference in glucose at 158 min of exercise and at exhaustion, no significant differences were found between drinks for any of the variables studied (P > or = .05). Ingestion of 13 g carbohydrate per hour is not sufficient to maintain plasma glucose, attenuate the glucoregulatory hormone response, and improve performance during prolonged moderate intensity cycling.
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PMID:Failure of low dose carbohydrate feeding to attenuate glucoregulatory hormone responses and improve endurance performance. 166 7

This study provides the first experimental evidence of the short-term control of fructose 2,6-bisphosphate (Fru(2,6)P2) levels in adult human hepatocytes. (1) In hepatocytes whose metabolic status resembles the fed state (glycogen-rich), exposure to glucagon (10(-8) M) caused a drastic decrease in the levels of this effector and a significant fall in lactate production rate. Adrenaline, isoprenaline (a beta-adrenergic agonist) and lactate exerted a similar action decreasing Fru(2,6)P2 concentration. (2) In glucagon pre-treated, glycogen- and Fru(2,6)P2-depleted cells (a situation that mimics the fasted state), Fru(2,6)P2 re-synthesis was strictly dependent on glucose availability. (3) Insulin did not seem to exert a direct action on the control of Fru(2,6)P2 in human hepatocytes. The hormone--which failed to enhance Fru(2,6)P2 in glucose-starved cells--did not further increase Fru(2,6)P2 content nor its time-course evolution as compared to hepatocytes incubated with glucose alone. (4) Lactate caused a significant delay in the glucose-induced increase in Fru(2,6)P2 content that could not be prevented by insulin. (5) Data indicate that in human hepatocytes glucose is a more powerful modulator of Fru(2,6)P2 than insulin, and that variations in blood lactate concentration may also play a role in the control of hepatic Fru(2,6)P2 levels during the fasted-to-fed transition in humans.
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PMID:Glucose: a more powerful modulator of fructose 2,6-bisphosphate levels than insulin in human hepatocytes. 189 1

Plasma glucose, insulin, glucagon, free fatty acid, ketone body, lactate and pyruvate were measured in 14 patients undergoing gastrectomy under general anesthesia with nitrous oxide and oxygen. Lactated ringer solution with glucose load (10 g.hr-1) was administered in seven patients [glucose loading group: Glucose (+)] and the other seven patients received only lactated ringer solution [glucose free group: Glucose (-)]. Blood glucose increased significantly in both groups, but a significant difference appeared between Glucose (+) and Glucose (-). Plasma insulin activity and IRI/BS ratio increased in Glucose (+) and a significant difference was found between the two groups. No remarkable change in plasma glucagon level was found in both groups. Free fatty acid and ketone bodies (acetoacetate, beta-hydroxybutyrate) decreased significantly in Glucose (+), but they increased significantly in Glucose (-) and significant differences were found between the two groups. The rate of changes of beta-hydroxybutyrate was consistently higher than that of acetoacetate. Lactate and pyruvate increased significantly in both groups. These results suggest that continuous glucose loading may facilitate insulin release from the pancreas and suppress the hyperketonemia and hyperlipidemia during partial gastrectomy.
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PMID:[The effect of glucose loading on changes in ketone and glucose metabolism during gastrectomy]. 236 42

The effect of different immunosuppressive drugs (prednisolone, azathioprine, cyclosporin A) on liver carbohydrate metabolism in the rat was investigated. Daily administration of prednisolone (3 mg/kg body weight) and azathioprine (2 mg/kg body weight) intraperitoneally for 2 weeks caused significantly lower liver glycogen content than that in NaCl-treated controls. Liver glucose and lactate content, as well as plasma glucose, glucagon, and serum insulin concentration of these animals, remained unchanged. There were no differences in any of these parameters between cyclosporin A (15 mg/kg body weight)-treated and vehicle (olive oil/ethanol)-treated animals. Prednisolone caused significantly lower glucose production in isolated rat hepatocytes using Na-pyruvate as the substrate, whereas glucose production was unchanged in hepatocytes of azathioprine-treated rats using pyruvate or L-serine as substrates. Glucose production from pyruvate or serine was significantly inhibited by cyclosporin A compared to the vehicle, but did not differ from the effects of azathioprine and prednisolone. Lactate production was significantly lower in cyclosporin-treated animals than in those given either the vehicle or azathioprine. Cyclosporin A completely reversed the inhibition of hepatocyte glycogen consumption caused by the vehicle. However, glycogen production in the presence of cyclosporin A was comparable to the effects of prednisolone and azathioprine. Finally, hepatocyte ketone body production using pyruvate as the substrate was higher in the presence of all immunosuppressive drugs. In the presence of serine, acetoacetate production increased in rats treated with 50 mg/kg body weight cyclosporin A, and beta-hydroxybutyrate production in animals receiving 15 and 50 mg/kg body weight cyclosporin A.
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PMID:Effect of cyclosporin A, azathioprine, and prednisolone on carbohydrate metabolism of rat hepatocytes. 236 76

The effects of different thyroid states on glucagon/dBcAMP-induced gluconeogenesis from alanine or lactate were investigated in the isolated perfused liver from 24-hr starved rats. Gluconeogenesis from alanine varied with the thyroid state, being increased in hyperthyroidism and decreased in hypothyroidism. Both glucagon and dBcAMP increased glucose production from alanine in euthyroid and even less pronounced in hypothyroid livers, the effect was dose dependent; concomitantly alanine and [14C] alpha-amino-isobutyric acid uptake increased. In hyperthyroid liver, both glucagon and dBcAMP stimulated neither hepatic uptake of alanine and [14C] alpha-amino-isobutyric acid nor gluconeogenesis from alanine. Lactate uptake as well as glucose production from lactate varied with the thyroid state, being increased in the hyper- and decreased in the hypothyroid state. Both glucagon and dBcAMP increased lactate uptake as well as gluconeogenesis from lactate: the effect was even more pronounced in hyperthyroid and reduced in hypothyroid liver. We conclude that the glucogenic effect of glucagon/dBcAMP is reduced in the hypo- and--at unlimited substrate supply--stimulated in the hyperthyroid liver.
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PMID:Interrelation between thyroid state and the effect of glucagon on gluconeogenesis in perfused rat livers. 243 88


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