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)

1. The subcellular distribution of adenine nucleotides, acetyl-CoA, CoA, glutamate, 2-oxoglutarate, malate, oxaloacetate, pyruvate, phosphoenolpyruvate, 3-phosphoglycerate, glucose 6-phosphate, aspartate and citrate was studied in isolated hepatocytes in the absence and presence of glucagon by using a modified digitonin procedure for cell fractionation. 2. In the absence of glucagon, the cytosol contains about two-thirds of cellular ATP, some 40-50% of ADP, acetyl-CoA, citrate and phosphoenolpyruvate, more than 75% of total 2-oxoglutarate, glutamate, malate, oxaloacetate, pyruvate, 3-phosphoglycerate and aspartate, and all of glucose 6-phosphate. 3. In the presence of glucagon the cytosolic space shows an increase in the content of malate, phosphoenolpyruvate and 3-phosphoglycerate by more than 60%, and those of aspartate and glucose 6-phosphate rise by about 25%. Other metabolites remain unchanged. After glucagon treatment, cytosolic pyruvate is decreased by 37%, whereas glutamate and 2-oxoglutarate decrease by 70%. The [NAD(+)]/[NADH] ratios calculated from the cytosolic concentrations of the reactants of lactate dehydrogenase and malate dehydrogenase were the same. Glucagon shifts this ratio and also that of the [NADP(+)]/[NADPH] couple towards a more reduced state. 4. In the mitochondrial space glucagon causes an increase in the acetyl-CoA and ATP contents by 25%, and an increase in [phosphoenolpyruvate] by 50%. Other metabolites are not changed by glucagon. Oxaloacetate in the matrix is only slightly decreased after glucagon, yet glutamate and 2-oxoglutarate fall to about 25% of the respective control values. The [NAD(+)]/[NADH] ratios as calculated from the [3-hydroxybutyrate]/[acetoacetate] ratio and from the matrix [malate]/[oxaloacetate] couple are lowered by glucagon, yet in the latter case the values are about tenfold higher than in the former. 5. Glucagon and oleate stimulate gluconeogenesis from lactate to nearly the same extent. Oleate, however, does not produce the changes in cellular 2-oxoglutarate and glutamate as observed with glucagon. 6. The changes of the subcellular metabolite distribution after glucagon are compatible with the proposal that the stimulation of gluconeogenesis results from as yet unknown action(s) of the hormone at the mitochondrial level in concert with its established effects on proteolysis and lipolysis.
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PMID:Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. 19 59

Rat hepatocytes have been studied in suspension culture for 10-h periods. Levels of extractable lactate dehydrogenase (LDH) have been measured in these hepatocytes at hourly intervals in order to note the balance between biosynthesis and degradation of this enzyme. Newly synthesized LDH has been measured by following the rate of incorporation of [3H]leucine into radiochemically pure LDH of high specific catalytic activity as isolated by a rapid affinity chromatographic procedure. The effects of the addition of physiological concentrations of the following hormones at the beginning of 10-h culture periods immediately following preparation of the hepatocytes by the collagen perfusion procedure have been recorded. The hormones triiodothyronine (T3), insulin, glucagon, and dexamethasone have been added singly or in combination. The culture medium has supplied variable amounts of these hormones in the 10% of fetal calf (or other) serum added, and the hepatocytes themselves have provided intracellular amounts of hormones. In addition to the added hormones, N6,O2'-dibutyryl cyclic AMP (Bt2cAMP) has also been studied. Control suspensions of hepatocytes show reproducible initial levels of extractable LDH which are maintained or slightly increased during 10 h. Such control systems also incorporate [3H]leucine into total protein and into highly purified LDH at reproducible rates during 10 h of incubation. The effects of added hormones on LDH lavels are as follows: (a) T3 causes about a 2-fold increase in LDH at 7 to 8 h in hepatocytes from young adult animals, an effect which is lowered in either younger or older animals or in thyroidectomized animals. (b) Insulin leads to a similar increase in LDH at 5 to 6 h and a falling off at 8 to 10 h. (c) Glucagon also causes an approximate doubling of the amount of extractable LDH during a 10-doubling of the amount of extractable LDH during a 10-h period. (d) Dexamethasone does not produce an increase. (e) Bt2-cAMP produces an effect indistinguishable from that of glucagon. Paired combinations of these hormones fail to produce an additive response in any case. The combinations of T3 plus dexamethaseon and insulin plus dexamethasone lead to significant reductions in levels of extractable LDH when compared to the single hormone effects cited above. With respect to rates of synthesis of total protein as measured by [3H]leucine incorporation, only glucagon, glucagon plus Bt2-cAMP, glucagon plus insulin, T3 plus Bt2cAMP, and T3 plus insulin produce significant increases during a 10-h period. However, when [3H]leucine incorporation into highly purified LDH is measured as an index of LDH biosynthesis, T3, insulin, and glucagon consistently increase the biosynthetic rates during a 10-h period. Bt2cAMP produces a smaller increase. Dexamethasone fails to produce any significant change when compared to controls. Paired combinations of hormones again do not produce any additive effect on LDH biosynthesis when the hormone producing the higher level is taken as the reference...
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PMID:Hormonal effects on the biosynthesis of lactate dehydrogenase in rat hepatocytes. 22 47

The hepatic tolerability of phthalazine-(2,2-b)-phthalazin-5,12-(7H,14H)-dione (diftalone--administered at the dosage of 750 mg/day p.o. for a mean period of 23 days--has been studied in 40 patients by means of: total plasma protein, albumin, fibrinogen, serum glutamin-oxalacetic transaminase, serum glutamic-pyruvic transaminase, lactic dehydrogenase, creatine phosphokinase, alkaline phosphatase, glycemic curve after glucagon and plasmatic elimination of bromosulphalein. A statistically but not clinically significant increase of the SGPT level is the only change observed.
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PMID:Some laboratory aspects of hepatic tolerability of diftalone. 57 43

Streptozotocin treatment (125 mg/kg) in the Chinese hamster induced hyperglycaemia, hypoinsulinaemia, hyperglucagonaemia and changes in body, liver, pancreas, stomach, kidney and adipose tissue weights. The pancreatic reserves of insulin and glucagon in the diabetic animals were low, but stomach glucagon high. These animals showed high levels of phosphoenolpyruvate carboxykinase and low levels of glucokinase, hexokinase, isocitrate dehydrogenase and malic enzyme, but normal levels of pyruvate kinase in the liver. Increases in lactate dehydrogenase subunit B and isozymes 2, 3 and 4 were also observed in the liver, but not in the epididymal fat pad, of the diabetic animals. N-Acetyl-beta-D-glucosaminidase was elevated in plasma, liver and heart, but not in the kidney of the treated animals. Renal alpha-galactosidase and beta-glucosidase were depressed, whereas beta-galactosidase and alpha-glucosidase remained essentially normal. These features indicated that there were considerable differences between the biochemical disorders associated with streptozotocin-diabetes in the Chinese hamster and the published observations in the rat.
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PMID:Streptozotocin-induced diabetes in the Chinese hamster. Biochemical and endocrine disorders. 59 Jun 51

The glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK) gene is modulated by oxygen. It was proposed that heme proteins might function as O2 sensors; their actions are impaired after replacement of the central Fe2+ ion by Co2+ and inhibition of heme synthesis by succinylacetone (SA). Therefore, the effects of CoCl2 and SA, alone and in combination, on the glucagon-dependent induction of PCK activity and PCK mRNA were investigated at different physiological oxygen tensions in primary rat hepatocyte cultures. The cells were exposed to 50 microM CoCl2 and/or 2 mM SA from 4-24 h. After addition of fresh media without CoCl2 or SA, PCK was induced with 1 nM glucagon. PCK activity and PCK mRNA were elevated to 100% at 16% O2 and to about 65% at 8% O2. CoCl2 reduced these increases to about 45% at 16% O2 and to about 35% at 8% O2. SA lowered the inductions to about 50% and 40% each at 16% and 8% O2. CoCl2 plus SA diminished the elevations to about 5% at both oxygen tensions. In the presence of CoCl2 and/or SA, ornithine decarboxylase induction by insulin was not impaired; lactate dehydrogenase did not leak from the cells, which in electron microscopical inspections had normal cell structures. These findings support the hypothesis that a heme protein is involved in the activation of the PCK gene and that it acts as an O2 sensor.
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PMID:Modulation of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene by oxygen in rat hepatocyte cultures. Evidence for a heme protein as oxygen sensor. 139 23

Isoproterenol, epinephrine, phenylephrine and glucagon inhibited proteolysis in isolated perfused rat hearts. All of these agents had a positive inotropic effect, while isoproterenol and glucagon were shown to increase cyclic AMP content. The catecholamines, but not glucagon, partially depleted the adenine nucleotide pool, but the creatine-phosphate/creatine ratio was unchanged or increased. Isoproterenol markedly increased lactate production and caused release of lactate dehydrogenase. The effects of isoproterenol on these parameters, including proteolysis, were blocked by propranolol and verapamil. Isoproterenol also inhibited proteolysis when perfusate calcium was reduced from 2.5 to 0.5 mM; but, in this circumstance, isoproterenol did not deplete ATP. In hearts arrested with tetrodotoxin, neither isoproterenol nor glucagon inhibited proteolysis and neither of them depleted ATP. Both hormones still increased cyclic AMP content. These findings suggest that cyclic AMP may not be involved in the control of proteolysis, and that the effects of isoproterenol and glucagon are mediated via effects on contractility. The studies stress the importance of preventing adenine nucleotide depletion and controlling contractility in experiments on the mechanisms of inotropic agents on cardiac protein turnover.
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PMID:Catecholamines, glucagon, energy metabolism and protein degradation in rat heart. 196 72

Isolation of pure acinar cells of the rat pancreas was achieved employing counterflow sedimentation filtration technique (CSFT). The preparation of purified acinar cells contained an occasional red blood cell (RBC, 200:1) with total absence of endocrine and duct cells. A significant stimulation of amylase secretion from isolated pure acinar cells was produced by octapeptide of cholecystokinin (CCK8) and insulin produced potentiation of the effect of CCK8. Synthetic glucagon inhibited basal and CCK8 stimulated amylase secretion. Non-synthetic purified glucagon stimulated amylase secretion and potentiated the effect of CCK8. Vasoactive intestinal polypeptide (VIP) did not stimulate amylase secretion but potentiated the effect of CCK8. No leakage of lactic dehydrogenase (LDH) was detected from the cells in any of the secretion studies. Thus a highly purified preparation of isolated pure acinar cells of rat pancreas could be obtained with excellent morphologic and functional integrity.
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PMID:Amylase secretion from isolated pure acinar cells. 240 20

It is well established that caloric restriction extends life span and significantly retards the rate of occurrence of most age-associated degenerative disease processes. A paucity of data exists relative to the mechanisms by which caloric restriction accomplishes these events. We have examined the effect of caloric restriction in rats on several hepatic enzymes of intermediary metabolism. The activities of glycolytic and supporting enzymes including lactate dehydrogenase, pyruvate kinase, sorbitol dehydrogenase, and alcohol dehydrogenase were all decreased in response to caloric restriction. Fructose 1-phosphate aldolase and creatine phosphokinase were not altered. Likewise, enzymes associated with lipid metabolism (malic enzyme and glycerokinase) were reduced (fatty acid synthetase was reduced, but not to a statistically significant degree). Activities of enzymes supporting gluconeogenesis (glutamate oxaloacetate transaminase, tyrosine aminotransferase, glutamate pyruvate transaminase, glutamate dehydrogenase, amino acid oxidase, malate dehydrogenase, and glucose 6-phosphatase) were either unchanged or increased significantly by caloric restriction. Glucagon levels were decreased. Comparisons between young ad libitum fed and older calorically restricted rats revealed similar but not identical metabolic activity. These results suggest that caloric restriction produces an effect on intermediary metabolism, favoring the role of glucagon and glucose synthesis; but limiting the role of insulin and glucose catabolism in the liver. The former observation provides for the efficient support of peripheral tissues and the latter a level of energy production necessary only for self maintenance. Limited lipid metabolism suggests decreased potential for fatty acid epoxide formation and free radical damage to cellular macromolecules. Additionally, caloric restriction may delay the progressive age associated changes in the activities of some of the enzymes investigated.
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PMID:Effect of chronic caloric restriction on hepatic enzymes of intermediary metabolism in the male Fischer 344 rat. 266 33

(i) Hepatocytes isolated from adult rats were cultured for 2 to 3 weeks on collagen in a modified, serum-free Waymouth medium containing fatty acids and varying concentrations of glucocorticoid, insulin and glucagon. (ii) In the presence of all three hormones, it was possible to maintain the content of DNA, the activity of glucokinase, pyruvate kinase, hexokinase and lactate dehydrogenase at initial levels for 2 to 3 weeks. The activity of glucokinase and pyruvate kinase was affected by the concentration of insulin. (iii) The activity of alcohol dehydrogenase was stable for 3 days and declined to about 25% of the initial level after 2 weeks of culture, irrespective of the presence of hormones. (iv) Maintenance of albumin secretion was dependent on the presence of glucocorticoid, and glucocorticoid and insulin showed an additive or, at some time points, a synergistic effect on its secretion. (v) The content of cytochrome P-450 could be kept at 65% of the initial level, provided that a relatively high concentration of dexamethasone was present (10(-6) M). (vi) In the absence of hormones, urea synthesis was 70% of initial levels throughout the experimental period. With insulin and glucocorticoid present, a high concentration of glucagon (10(-8) M) was required to maintain the synthesis of urea at this level. (vii) It is concluded that hepatocyte cultures as described in the present study may be a useful, well-defined system for long-term metabolic, pharmacologic and toxicologic studies.
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PMID:Long-term culture of hepatocytes: effect of hormones on enzyme activities and metabolic capacity. 327 89

Rat hepatocytes were cultured in a modified HI-WO/BA medium for 13 days, and the combined effect of dexamethasone, 10(-7) M, insulin, 10(-8) M, and glucagon, 10(-9) M on the DNA-content, and on the activity of several enzymes, the secretion of albumin and the rate of ethanol oxidation was investigated. The effect of ethanol on these parameters was also studied. All parameters measured declined with time in the hormone-free cultures. In hormone-supplemented cultures, the DNA-content, the activity of glucokinase, pyruvate kinase, hexokinase and lactate dehydrogenase and the secretion of albumin was maintained at reasonable levels throughout the 13 days, whereas both the activity of alcohol dehydrogenase and the rate of ethanol oxidation fell significantly, although less than in hormone-free cultures. Addition of 50 mM ethanol to the hormone-supplemented culture medium caused a ca. 20% fall in the activity of glucokinase and pyruvate kinase and a 20% increase in alcohol dehydrogenase activity. No effect of ethanol was observed on the activity of hexokinase and lactate dehydrogenase or on the secretion of albumin.
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PMID:Long-term culture of hepatocytes: ethanol oxidation and effect of ethanol on enzyme activities and albumin secretion. 332 6


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