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)

The effect of treatment of rats with bacterial endotoxin on fructose 2,6-bisphosphate (Fru-2,6-P2) metabolism was investigated in isolated liver cells prepared from 18 h-starved animals. The results obtained support the hypothesis that a stimulation of 6-phosphofructo-1-kinase (PFK-1) activity and an inhibition of fructose-1,6-bisphosphatase (Fru-1,6-P2ase) may be one mechanism underlying the inhibition of gluconeogenesis from lactate and pyruvate by endotoxin. We suggest that the stimulation of PFK-1 and inhibition of Fru-1,6-P2ase activity is the result of a 2-3-fold increase in Fru-2,6-P2. The latter is not due to changes in the total activity or phosphorylation state of the bifunctional 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase, but appears to be the result of a decrease in the cytosolic concentration of phosphoenolpyruvate (PEP), an inhibitor of PFK-2 activity. The effect of endotoxin is resistant to the presence of glucagon, which has comparable effects in cells prepared from both control and endotoxin-treated animals. The mechanism by which endotoxin treatment of the rat decreases PEP and gluconeogenesis remains to be established. However, it does not involve alterations in either the total activity or the phosphorylation state of pyruvate kinase, nor does it involve increased flux through this enzyme in the intact cell, which is in fact decreased in this model of septic shock. It is suggested that the decreased flux may result from a lower rate of formation of PEP, suggesting that the prime lesion in sepsis is an inhibition of one or more of the steps leading to PEP formation.
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PMID:Effect of treatment in vivo of rats with bacterial endotoxin on fructose 2,6-bisphosphate metabolism and L-pyruvate kinase activity and flux in isolated liver cells. 132 Mar 77

The effects of tolbutamide on the activities of fructose-6-phosphate,2-kinase and fructose-2,6-bisphosphatase were examined using rat hepatocytes. Tolbutamide stimulated fructose-6-phosphate,2-kinase activity and inhibited fructose-2,6-bisphosphatase activity, resulting in an increase of fructose-2,6-bisphosphate level. Changes in the activities of the enzyme by tolbutamide were due to variation in the Km value, but not dependent on alteration of Vmax. Glucagon inhibition of fructose-2,6-bisphosphate formation resulting from an inactivation of fructose-6-phosphate,2-kinase and an activation of fructose-2,6-bisphosphatase was released by tolbutamide. Tolbutamide stimulation of fructose-2,6-bisphosphate formation through regulation of fructose-6-phosphate,2-kinase/fructose-2,6-bisphosphatase may produce enhancement of glycolysis and inhibition of gluconeogenesis in the liver.
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PMID:Effect of tolbutamide on fructose-6-phosphate,2-kinase and fructose-2,6-bisphosphatase in rat liver. 302 Nov 37

A new activator of phosphofructokinase, which is bound to the enzyme and released during its purification, has been discovered. Its structure has been determined as beta-D Fructose-2,6-P2 by chemical synthesis, analysis of various degradation products and NMR. D-Fructose-2,6-P2 is the most potent activator of phosphofructokinase and relieves inhibition of the enzyme by ATP and citrate. It lowers the Km for fructose-6-P from 6 mM to 0.1 mM. Fructose-6-P,2-kinase catalyzes the synthesis of fructose-2,6-P2 from fructose-6-P and ATP, and the enzyme has been partially purified. The degradation of fructose-2,6-P2 is catalyzed by fructose-2,6-bisphosphatase. Thus a metabolic cycle could occur between fructose-6-P and fructose-2,6-P2, which are catalyzed by these two opposing enzymes. The activities of these enzymes can be controlled by phosphorylation. Fructose-6-P,2-kinase is inactivated by phosphorylation catalyzed by either cAMP dependent protein kinase or phosphorylase kinase. The inactive, phospho-fructose-6,P,2-kinase is activated by dephosphorylation catalyzed by phosphorylase phosphatase. On the other hand, fructose-2,6-bisphosphatase is activated by phosphorylation catalyzed by cAMP dependent protein kinase. Investigation into the hormonal regulation of phosphofructokinase reveals that glucagon stimulates phosphorylation of phosphofructokinase which results in decreased affinity for fructose-2,6-P2 appears to be due to the decreased synthesis by inactivation of fructose-2,6-P2,2-kinase and increased degradation as a result of activation of fructose-2,6-bisphosphatase. Such a reciprocal change in these two enzymes has been demonstrated in the hepatocytes treated by glucagon and epinephrine. The implications of these observations in respect to possible coordinated controls of glycolysis and glycogen metabolism are discussed.
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PMID:Fructose-2,6-P2, chemistry and biological function. 629 99

Effect of tolbutamide on liver fructose-2,6-bisphosphate (F-2,6-P2) was examined in isolated perfused rat liver in situ with a flow-through method. Tolbutamide (1 mM) gradually increased liver F-2,6-P2 level from 7.4 +/- 1.6 to 21.2 +/- 1.6 pmol/mg wet wt for 20 min perfusion. The increase of liver F-2,6-P2 induced by tolbutamide was dose dependent and was significantly observed at 10 min perfusion. The maximum plateau level of F-2,6-P2 induced by 16.7 mM glucose was further increased with 1 mM tolbutamide. Glucagon (10(-11) M) decreased the elevated level induced by 16.7 mM glucose, but this effect was completely inhibited with 2 mM tolbutamide. Cyclic AMP level of the liver throughout the perfusion with tolbutamide did not change. Carboxytolbutamide or gliclazide perfusion did not change significantly the liver F-2,6-P2 level; however, the results suggest that tolbutamide may increase the liver F-2,6-P2 level by affecting the phosphorylation state of fructose-6-phosphate, 2-kinase/fructose-2,6-bisphosphatase through cyclic AMP-dependent protein kinase, resulting in the stimulation of glycolysis and the inhibition of gluconeogenesis in the liver. Thus, the extrapancreatic action and the mechanism of action of different sulfonylureas may differ.
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PMID:Tolbutamide stimulates fructose-2, 6-bisphosphate formation in perfused rat liver. 654 2

In previous studies, we demonstrated that tolbutamide inhibits a phosphorylation of hepatic 6-phosphofructo-2-kinase (6PF-2-K)/fructose-2,6-bisphosphatase (Fru-2,6-P2ase) catalyzed by the adenosine 3',5'-cyclic monophosphate-dependent protein kinase in a reconstruction system using the purified enzyme from the rat liver. In the current study, to assess a role of tolbutamide on hepatic 6PF-2-K/Fru-2,6-P2ase physiologically, we used intact rat hepatocytes and examined effects of tolbutamide on a phosphorylation of the bifunctional enzyme in the presence of glucagon. Glucagon induced a rapid phosphorylation of hepatic 6PF-2-K/Fru-2,6-P2ase accompanied by an inhibition of 6PF-2-K activity and a stimulation of Fru-2,6-P2ase activity in a dose-dependent manner. Tolbutamide inhibited glucagon-induced phosphorylation of the bifunctional enzyme protein in a dose-dependent manner. By adding 2 mM tolbutamide, reduced activity of 6PF-2-K and increased activity of Fru-2,6-P2ase in the presence of 10(-9) M glucagon were partially restored. The present results suggest the possibility that tolbutamide modulates the activity of hepatic 6PF-2-K/Fru-2,6-P2ase through inhibiting a phosphorylation of the enzyme protein. The counterregulatory influence of tolbutamide on the effect of glucagon suggests a possible mechanism for the extrapancreatic effect of sulfonylurea drugs.
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PMID:Tolbutamide inhibits glucagon-induced phosphorylation of 6PF-2-K/Fru-2,6-P2ase in rat hepatocytes. 790 Jul 85

We have developed a new quantification method to measure translocation of glucokinase between nucleus and cytoplasm in primary hepatocytes. The method is robust, reliable and sensitive with the use of a high content fluorescence microscope, which can analyse more than 20,000 hepatocytes under each experimental condition. Frequency distributions of the nuclear and cytoplasmic contents of glucokinase did not exhibit a Gaussian distribution. Moreover, the distributions have large standard deviation values compared with their average values. These results indicate that a large number of cells must be analysed for the accurate quantification. Glucose and sorbitol promoted the translocation of glucokinase from nucleus to cytoplasm. These results show good agreement with previous reports. However, glucagon did not affect the localization of glucokinase. Under the same conditions, liver-type isozyme of fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase (F6P2K), whose dephosphorylated form has been proposed as a cytoplasmic binding protein with glucokinase, was completely phosphorylated. These results indicate that the phosphorylation and dephosphorylation of F6P2K does not have any appreciable effect on the intracellular localization of glucokinase.
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PMID:Quantitative image analysis reveals that phosphorylation of liver-type isozyme of fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase does not affect nuclear translocation of glucokinase in rat primary hepatocytes. 2084 23