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)

Using rat hepatocytes we confirmed our previous results that glucagon and beta-adrenergic agonists increased the enzyme activity of alanine aminotransferase (AAT) and propranolol abolished their effects. Only the enzyme activity was measured and other parameters like quantity of the enzyme or activation due to modification were not looked for. As in perfusion experiment phenylephrine and phenoxybenzamine (alpha-agonist and alpha-antagonist respectively) also alpha-antagonist respectively) also increased the AAT activity in isolated rat hepatocytes and propranolol reversed these effects. The additive effect of glucagon and phenoxybenzamine on AAT was also persistent in hepatocyte system. Fructose-1:6-bisphosphatase (Fru-P2-ase), another key enzyme in gluconeogenic pathway, was elevated by glucagon and other beta-adrenergic agonists both in liver perfusion and isolated hepatocyte experiments and was brought back to the normal level by propranolol. In this case also only the enzyme activity was measured and no other parameters were looked for. Unlike AAT this enzyme was not stimulated by phenylephrine or phenoxybenzamine. But AAT and Fru-P2-ase activities were increased significantly by adenylate cyclase activators like fluoride or forskolin. Thus, it appears that the regulation of fru-P2-ase by glucagon is purely a b-receptor mediated process whereas AAT activation shows a mixed type of regulation where some well known alpha-agonist and antagonists are behaving as beta-agonists. Results further indicate the presence of phosphodiesterase in hepatocyte membrane which was stimulated by glucagon and brought back to the normal level by propranolol. The different adrenergic compounds stated above, not only modified the activity of the above two enzymes but also stimulated glucose production by hepatocytes from alanine which was in turn abolished by propranolol as well as amino oxyacetate (AOA), a highly specified inhibitor of AAT. This confirm the participation of AAT in gluconeogenesis from alanine in liver. Forskolin and fluoride also increased the glucose production from alanine and showed additive effects with glucagon, phenylephrine and phenoxybenzamine.
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PMID:Effect of adrenergic agonists and antagonists on alanine amino transferase, fructose-1:6-bisphosphatase and glucose production in hepatocytes. 135 93

Administration of vasopressin and glucagon evokes a transient release of Ca2+ from perfused livers. The Ca2+ is released from a pool that is depletable by the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). Therefore, the mechanism of the FCCP-stimulated Ca2+ release was examined. The FCCP-stimulated Ca2+ release was associated with a decrease in ATP levels. In the presence of oligomycin, which blocked the FCCP-induced rapid ATP breakdown, FCCP did not release Ca2+ though it still stimulated respiration. The possibility that FCCP might indirectly cause a release of Ca2+ by lowering hepatic ATP was examined at two levels of organization: 1) in the whole organ, by perfusing livers with fructose, a compound that was shown previously to drastically lower ATP in the liver, and 2) in isolated microsomal vesicles by depleting ATP with glucose and hexokinase. Fructose evoked Ca2+ release from the perfused liver. Similarly, depletion of ATP by the addition of glucose and hexokinase evoked a rapid release of the accumulated Ca2+ from microsomal vesicles probably by the inhibition of the Ca2(+)-ATPase. These results demonstrate that the major mechanism by which FCCP releases Ca2+ in intact cells is by lowering ATP levels.
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PMID:Hormonal stimulation of Ca2+ release from the perfused liver: effects of uncoupler. 210 59

Kinetic characteristics of American eel liver 6-phosphofructo-1-kinase (PFK-1) and the effects of porcine insulin, bovine glucagon, and dibutyryl-cAMP were studied. At 0.1 mM ATP, kinetics were sigmoidal with respect to fructose-6-phosphate (F-6-P) concentrations and the S0.5 (F-6-P) increased with higher ATP concentrations. At 2 mM F-6-P, optimal ATP concentrations were 0.1 mM, with maximal inhibition at 0.5 mM. Fructose 2,6-bisphosphate (Fru-2,6-P2) offset ATP inhibition and activated the enzyme, changing F-6-P kinetic curves from sigmoidal to hyperbolic. At 2 mM F-6-P and 0.1 mM ATP the Fru-2,6-P2 activation curve was hyperbolic with a Ka of approximately 1 microM. In isolated hepatocytes, porcine insulin decreased the sensitivity of PFK-1 to ATP, an effect that was offset when bovine glucagon was also present. Insulin, alone and with glucagon, increased the Fru-2,6-P2 activation ratio. In the presence of glucagon, insulin increased Fru-2,6-P2 concentrations in hepatocytes. These effects suggest that PFK-1 is a potential regulatory point for hormones in the control of carbohydrate metabolism in the American eel liver.
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PMID:The regulation of 6-phosphofructo-1-kinase by insulin and glucagon in isolated hepatocytes of the American eel. 253 79

Dietary carbohydrates are known to stimulate L-type pyruvate kinase gene expression at the transcriptional level in the liver. However, the short-term effects, the time course, and the mechanism of the gene activation by elemental hexoses in normal fasted rats remain unknown. In the present study, both glucose and fructose were found to stimulate the gene expression at the transcriptional level in liver. However, the kinetics and the extent of the mRNA induction differed according to the carbohydrate given. Fructose stimulated early (2-4 h) and transiently the gene transcription, the RNA precursor, and the mRNA accumulation in 48-h-fasted rats while maximum stimulation of the RNA synthesis by glucose was delayed until the 12th h of refeeding, despite an early rise of plasma insulin. In contrast, insulin release was not required for fructose to trigger the gene transcription, nor did the high cyclic AMP levels in fasted rat liver prevent RNA synthesis by fructose. The agent(s) operating early in fructose-fed animals might be powerful enough to not require insulin for gene activation and to balance the inhibitory action of glucagon in the liver.
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PMID:Differential effects of glucose and fructose on liver L-type pyruvate kinase gene expression in vivo. 282 12

We investigated the effect of several potential carbohydrate secretagogues, amino acids, a ketoacid, and potassium chloride on insulin, glucagon, and somatostatin release from the in vitro perfused Brockmann body of channel catfish (Ictalurus punctatus). Mannose (15 mM) stimulated the release of insulin and somatostatin. Fructose (30 mM) induced only a small and transient release of somatostatin. Galactose (15 mM) was not a secretagogue. Likewise, glyceraldehyde failed to stimulate hormone release. Among the amino acids newly tested, alanine and leucine, and also alpha-ketoisocaproic acid were without effect. A high concentration of potassium (25 mEq/liter) induced a pronounced release of insulin and glucagon and a moderate release of somatostatin. In conclusion, a striking similarity exists between catfish and higher vertebrates in their pancreatic endocrine response to hexoses; on the other hand, the catfish Brockmann body appears to respond only to a few of the common stimuli of pancreatic hormone release in mammals.
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PMID:Secretagogues for pancreatic hormone release in the channel catfish (Ictalurus punctatus). 288 40

The provision of small amounts of glucose during fasting is known to spare body protein and to attenuate markedly the metabolic response to starvation. These actions, which are not shared by fat, are generally thought to depend on the ability of exogenous glucose to stimulate insulin secretion. To determine whether fructose, a very weak insulin secretagogue, will also conserve nitrogen and alter the response to fasting, we infused small amounts of fructose, 100 g/d (375 kcal), into 7 obese subjects during a 10-day fast: 4 received fructose days 7 to 10, and 3 received fructose days 1 to 7. Fructose virtually abolished (all P less than 0.05-0.01) the fasting induced: (a) fall in glucose and insulin and rise in glucagon, (b) fall in triiodothyronine, (c) ketosis and acidosis, (d) increased ammonia excretion, (e) hyperuricemia (and hypouricosuria), and (f) fall in plasma alanine and rise in branched chain amino acids. Fructose also significantly reduced urinary sodium loss. Moreover, fructose exerted a prominent protein-sparing action, even though plasma insulin concentrations never exceeded postabsorptive levels. Excretion of total nitrogen was reduced by 40% to 50% during periods of fructose infusion, reflecting significant suppression of both urea and ammonia generation (all P less than 0.05-0.01). Most plasma glucogenic amino acids rose significantly during fructose administration. We conclude that low-dose fructose infusion essentially abolishes the entire hormone-substrate response to fasting, and spares body protein without raising insulin above postabsorptive levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitrogen conservation in starvation revisited: protein sparing with intravenous fructose. 351 Mar 63

1. Rates of glucose oxidation, lactate output and the intracellular concentration of glucose 6-phosphate were measured in mouse pancreatic islets incubated in vitro. 2. Glucose oxidation rate, measured as the formation of (14)CO(2) from [U-(14)C]glucose, was markedly dependent on extracellular glucose concentration. It was especially sensitive to glucose concentrations between 1 and 2mg/ml. Glucose oxidation was inhibited by mannoheptulose and glucosamine but not by phlorrhizin, 2-deoxyglucose or N-acetylglucosamine. Glucose oxidation was slightly stimulated by tolbutamide but was not significantly affected by adrenaline, diazoxide or absence of Ca(2+) (all of which may inhibit glucose-stimulated insulin release), by arginine or glucagon (which may stimulate insulin release) or by cycloheximide (which may inhibit insulin synthesis). 3. Rates of lactate formation were dependent on the extracellular glucose concentration and were decreased by glucosamine though not by mannoheptulose; tolbutamide increased the rate of lactate output. 4. Islet glucose 6-phosphate concentration was also markedly dependent on extracellular glucose concentration and was diminished by mannoheptulose or glucosamine; tolbutamide and glucagon were without significant effect. Mannose increased islet fructose 6-phosphate concentration but had little effect on islet glucose 6-phosphate concentration. Fructose increased islet glucose 6-phosphate concentration but to a much smaller extent than did glucose. 5. [1-(14)C]Mannose and [U-(14)C]fructose were also oxidized by islets but less rapidly than glucose. Conversion of [1-(14)C]mannose into [1-(14)C]glucose 6-phosphate or [1-(14)C]glucose could not be detected. It is concluded that metabolism of mannose is associated with poor equilibration between fructose 6-phosphate and glucose 6-phosphate. 6. These results are consistent with the idea that glucose utilization in mouse islets may be limited by the rate of glucose phosphorylation, that mannoheptulose and glucosamine may inhibit glucose phosphorylation and that effects of glucose on insulin release may be mediated through metabolism of the sugar.
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PMID:Glucose metabolism in mouse pancreatic islets. 491 69

Arterial (A) and renal venous (RV) concentrations and net splanchnic exchange of glucose, fructose, lactate, pyruvate, glycerol, and alanine were studied in the basal state and during a 135-min intravenous infusion of fructose at 2 mmol/min in healthy subjects after a 60-h fast. After 45 min of the fructose infusion, somatostatin (9 microgram/min) was infused for 60 min to induce hypoglucagonemia. Fructose infusion resulted in a net uptake of this hexose by the kidney as well as the splanchnic bed. Estimated renal uptake of fructose could account for the disposal of 20% of the administered fructose load while splanchnic uptake accounted for 38%. The fructose infusion resulted in a rise in blood glucose of 0.9 mmol/L, a 35% increase in net glucose output from the splanchnic bed, and a consistent net output of glucose from the kidney (A-RV = -0.17 +/- 0.05 mmol/L as compared with 0 +/- 0.03 in the basal state, P less than 0.02). Net glucose release from the kidney could account for 55% of the net renal uptake of fructose. The fructose infusion also resulted in a marked change in renal lactate balance from a net uptake in the basal state (A - RV = 0.05 +/- 0.01 mmol/L) to a net output during fructose administration (A - RV = -0.10 +/- 0.04). Administration of somatostatin resulted in a fall in arterial glucagon levels and a 35% decrease in splanchnic glucose output but failed to alter the arterial-renal venous difference for glucose observed during the fructose infusion. We conclude that in 60-h fasted man: (a) intravenous infusion of fructose results in a net uptake of this hexose by the kidney as well as the liver, (b) this uptake is accompanied by stimulation of renal as well as hepatic glucose production and renal production of lactate, and (c) hypoglucagonemia inhibits splanchnic but not renal glucose output during fructose infusion. These data indicate that the kidney is an important site of fructose disposal and that glucose and lactate are end products of renal fructose metabolism.
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PMID:Role of the kidney in the metabolism of fructose in 60-hour fasted humans. 613 22

Hormonal regulation of key gluconeogenic enzymes and glucose release by glucagon, dexamethasone, secretin and somatostatin was evaluated in maintenance cultured rat hepatocytes. (i) Phosphoenolpyruvate (PEP)-carboxykinase activity declined rapidly during the first 24 h in serum- and hormone-free culture with a further slight decay during the following 2 days. Dexamethasone and glucagon independently increased PEP-carboxykinase and acted synergistically when added in combination. Glucose-6-phosphatase activity declining linearly during hormone-free culture was stimulated by glucagon. Dexamethasone itself was without significant effects but completely abolished glucagon action. Fructose-1,6-diphosphatase was maintained at its initial level during the first day under control conditions and declined thereafter. Neither glucagon nor dexamethasone affected total activity or substrate (fructose-1,6-diphosphate) affinity of this enzyme. In short-term experiments on cells cultured under control conditions, protein synthesis-dependent stimulation of PEP-carboxykinase by glucagon and the permissive action of dexamethasone was demonstrated. Glucose-6-phosphatase and fructose-1,6-diphosphatase were not altered by hormones within this period. (ii) Stimulation by glucagon of gluconeogenesis was independent of its action on PEP-carboxykinase. Dexamethasone inhibited glycogenolysis but maintained glucose release at control levels probably by stimulation of gluconeogenesis. When added in combination, the glycogen-preserving action of dexamethasone acutely reduced the glucose release in response to glucagon. Glucagon sensitivity remained unchanged. (iii) The gastrointestinal hormones secretin and somatostatin were ineffective in modulating basal or glucagon-stimulated glucose release and gluconeogenic key enzymes. They are therefore unlikely to play a physiological role in hepatic glucose metabolism.
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PMID:Hormonal regulation of key gluconeogenic enzymes and glucose release in cultured hepatocytes: effects of dexamethasone and gastrointestinal hormones on glucagon action. 614 94

Fructose 2,6-bisphosphate, a known powerful stimulator of phosphofructokinase [Van Schaftingen, E., Hue, L. & Hers, H.-G. (1980) Biochem. J. 192, 897-901] was found to inhibit, at micromolar concentrations, liver and muscle fructose-1,6-biphosphate (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11). The main characteristics of this inhibition are that (i) it is much stronger at low than at high substrate concentrations, (ii) it changes the substrate saturation curve from almost hyperbolic to sigmoidal, and (iii) it is synergistic with the inhibition by AMP. This inhibition may play an important role in the stimulation of gluconeogenesis by glucagon, because this hormone is known to decrease the concentration of fructose 2,6-bisphosphate in the liver [Van Schaftingen, E., Hue, L. & Hers, H.-G. (1980) Biochem. J. 192, 887-895].
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PMID:Inhibition of fructose-1,6-bisphosphatase by fructose 2,6-biphosphate. 626 19


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