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 intravenous administration of glucagon to anesthetized rats resulted within 5 min in a 20% drop in the hepatic phosphorylase phosphatase activity, as measured in a post-mitochondrial supernatant at low dilution, but it did not affect the activity of glycogensynthase phosphatase. On the other hand, the injection of insulin plus glucose caused increases by about 35% in both phosphatase activities. Upon subcellular fractionation these effects were recovered in the cytosol, but not in the glycogen/microsomal fraction. However, activity changes in the latter fraction were observed after recombination with the liver cytosol from a hormone-treated animal. Preincubation of the liver cytosol with modulator protein (a specific inhibitor of type-1 protein phosphatases) cancelled the activity changes induced by insulin plus glucose. No hormonal effects on hepatic protein phosphatase activities were observed when the fractions were either diluted an additional 10-fold or pretreated with trypsin. An acute hormonal regulation of protein phosphatases could also be demonstrated in the perfused liver. When added to the perfusion medium, glucose as well as insulin increased the cytosolic protein phosphatase activities by about 25%. Their effect was additive, irrespective of the order of addition. On the other hand, the addition of glucagon and/or vasopressin resulted in a 20% drop in the phosphorylase phosphatase activity. The presence of glucagon did not interfere with the effectiveness of insulin, and vice versa. The changes in the phosphorylase phosphatase activities induced by glucagon, insulin, and glucose represented changes in the Vmax only. We propose that the acute control of the hepatic glycogen synthase phosphatase and phosphorylase phosphatase activities is mediated by transferable, cytosolic effector(s).
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PMID:Acute regulation of hepatic protein phosphatases by glucagon, insulin, and glucose. 284 53

The viability of the graft after liver transplantation is considered to be expressed as the sum of the hepatocellular activity by re-flowing of the hepatic blood flow after transplantation and the hepatocellular injury derived from the cold ischemia of the liver which is indispensable for transplantation. In order to elucidate the hepatocellular injury in ischemic liver graft cold ischemic liver model without hepatectomy was prepared and liver functions, serum insulin, glucagon and cyclic AMP after glucagon loading were measured. The following results were obtained. 1) Influence of anoxia due to ischemia of the liver expressed by s-GOT, disappeared 2 days after operation but it lasted for long time by s-GPT. Re-elevation of s-GOT, s-GPT observed after 2 days or more was considered to be derived from the hepatocellular necrosis due to rejection. Incidentally, Al-phosphatase was useful for judging the rejection, but s-total bilirubin, s-total cholesterol and albumin were considered to be not useful as parameters for evaluating the viability of the graft. 2) The rejection and the hepatocellular necrosis had not influence on serum insulin, but serum glucagon corresponded to the hepatocellular necrosis and was useful index for the judgment of the hepatocellular damage in the graft. 3) The level of c-AMP after glucagon loading and the c-AMP response corresponded very well to the hepatocellular activity of the graft, and they were considered to be useful indices for evaluating the viability of the graft.
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PMID:[Experimental study of orthotopic liver transplantation in dog--with reference to change of hepatic function, serum insulin, glucagon, c-AMP after liver transplantation and the viability of the graft]. 284 4

Interactions between the different signaling roles of myo-inositol 1,4,5-trisphosphate and 1,2-diacylglycerol, the products of agonist-stimulated phosphatidylinositol 4,5-bisphosphate breakdown, are assessed in isolated rat hepatocytes. Measurements of the kinetics of accumulation of individual [3H]inositol phosphates after the addition of different Ca2+-mobilizing agonists in general support the role of inositol 1,4,5-trisphosphate as the second messenger responsible for release of sequestered intracellular Ca2+. Various agonists, when added at maximal concentrations, however, produce qualitatively and quantitatively different responses, which reflect varying abilities of the agonists to activate phospholipase C. Qualitative differences are revealed by a pronounced biphasic pattern to the Ins(1,4,5)P3 accumulation after vasopressin and phenylephrine stimulation, which is indicative of negative feedback. It is suggested that this effect is mediated by a partial diacylglycerol activation of protein kinase C, which in vitro causes an activation of inositol phosphate 5-phosphatase and hence promotes removal of Ins(1,4,5)P3 to Ins(1,4)P2. An alternative mechanism proposed by Biden and Wollheim (1986) of a secondary Ca2+ activation of Ins(1,4,5)P3 3-kinase is considered less likely as a general mechanism, since highly purified kinase prepared from rat brain shows only an inhibition by Ca2+. Glucagon, 8-Br-cAMP, and EGF induce small increases of Ins(1,4,5)P3 in hepatocytes, together with slower and smaller increases of cytosolic free Ca2+ than those produced by vasopressin or phenylephrine, with Ca2+ being mobilized from the same intracellular pools with each of the agonists. The Ca2+-mobilizing effect of glucagon, therefore, may be entirely due to a cAMP-dependent process, although a direct receptor-mediated activation of phospholipase C, as suggested by Wakelam et al. (1986), remains a possibility. The EGF receptor appears to be coupled to phospholipase C, presumably via a G-protein. It is speculated that the mechanism by which cAMP increases Ins(1,4,5)P3 levels in hepatocytes could either be by phosphorylation and inhibition of inositol phosphate 5-phosphatase or by phosphorylation and facilitation of the coupling between the G-protein and phospholipase C. When protein kinase C is maximally activated by pretreatment of hepatocytes with PMA, the stimulatory effects of phenylephrine, glucagon, 8-Br-cAMP, and EGF on the accumulation of inositol phosphates and increase of cytosolic free Ca2+ are largely inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms involved in receptor-mediated changes of intracellular Ca2+ in liver. 285 Jun 13

When fasted rats were refed for 4 days with a carbohydrate and protein diet, a carbohydrate diet (without protein) or a protein diet (without carbohydrate), the effects of dietary nutrients on the fatty acid synthesis from injected tritiated water, the substrate and effector levels of lipogenic enzymes and the enzyme activities were compared in the livers. In the carbohydrate diet group, although acetyl-CoA carboxylase was much induced and citrate was much increased, the activity of acetyl-CoA carboxylase extracted with phosphatase inhibitor and activated with 0.5 mM citrate was low in comparison to the carbohydrate and protein diet group. The physiological activity of acetyl-CoA carboxylase seems to be low. In the protein diet group, the concentrations of glucose 6-phosphate, acetyl-CoA and malonyl-CoA were markedly higher than in the carbohydrate and protein group, whereas the concentrations of oxaloacetate and citrate were lower. The levels of hepatic cAMP and plasma glucagon were high. The activities of acetyl-CoA carboxylase and also fatty acid synthetase were low in the protein group. By feeding fat, the citrate level was not decreased as much as the lipogenic enzyme inductions. Comparing the substrate and effector levels with the Km and Ka values, the activities of acetyl-CoA carboxylase and fatty acid synthetase could be limited by the levels. The fatty acid synthesis from tritiated water corresponded more closely to the acetyl-CoA carboxylase activity (activated 0.5 mM citrate) than to other lipogenic enzyme activities. On the other hand, neither the activities of glucose-6-phosphate dehydrogenase and malic enzyme (even though markedly lowered by diet) nor the levels of their substrates appeared to limit fatty acid synthesis of any of the dietary groups. Thus, it is suggested that under the dietary nutrient manipulation, acetyl-CoA carboxylase activity would be the first candidate of the rate-limiting factor for fatty acid synthesis with the regulations of the enzyme quantity, the substrate and effector levels and the enzyme modification.
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PMID:Effects of dietary nutrients on substrate and effector levels of lipogenic enzymes, and lipogenesis from tritiated water in rat liver. 287 38

Acetyl-CoA carboxylase purified from isolated hepatocytes is activated dramatically by protein phosphatase treatment, concomitant with a reduction of the phosphate content from 3.7 to 1.1 mol/subunit. Glucagon treatment of the cells produces a further inactivation of the enzyme that is totally reversed by phosphatase treatment, and is associated with an increase in phosphate content of 0.8 mol/subunit, distributed in two peptides which contain the sites phosphorylated in vitro by the cyclic AMP-dependent and AMP-activated protein kinases. Sequencing of these peptides shows that the low activity of acetyl-CoA carboxylase is due to phosphorylation by the AMP-activated protein kinase, and not cyclic AMP-dependent protein kinase, even after glucagon treatment.
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PMID:The low activity of acetyl-CoA carboxylase in basal and glucagon-stimulated hepatocytes is due to phosphorylation by the AMP-activated protein kinase and not cyclic AMP-dependent protein kinase. 289 86

Fetal rat hepatocytes (22-day-old, full-term) in vivo were homogeneous in ultrastructure and glucose 6-phosphatase (G6Pase) distribution throughout the liver acinus. These cells were isolated and cultured for 17 days in Williams medium E containing 10% fetal calf serum, dexamethasone, insulin, and glucagon. Heterogeneity among hepatocytes appeared progressively during culture. There were variations in numbers of binucleated cells, cytoplasmic ultrastructure (e.g., in the distribution of glycogen and the quantity of ultrastructure (e.g., in the distribution of glycogen and the quantity of mitochondria), and intensity of histochemical reactivity for G6Pase. The cells could be classified generally into two types: type I cells had some characteristics of periportal hepatocytes and type II cells those of centrolobular hepatocytes in in vivo adult liver. The results show that a functional and structural heterogeneity can be formed among fetal hepatocytes in monolayer culture without differences in supply of oxygen, nutrients, and hormones. A hidden heterogeneity might already exist among hepatocytes in full-term fetuses even though it cannot be detected ultrastructurally or cytochemically.
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PMID:A functional and structural heterogeneity is formed among fetal rat hepatocytes during culture. 300 Feb 23

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

The effect of glucagon and insulin on rat liver phosphorylase phosphatase activity in vivo was investigated. The activity of phosphatase was found to decrease following the administration of glucagon and increase with insulin in a reversible manner. No change was detected in the activity of heat-stable phosphatase inhibitors in the hormone-treated samples. Liver protein kinases (regulatory subunit of cAMP-dependent protein kinase and/or Ca2+-dependent phosphorylase kinase) are suggested to regulate the activity of hepatic phosphorylase phosphatase (type 1 and 2A).
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PMID:Hormonal regulation of phosphorylase phosphatase activity in rat liver. 301 75

The kinetics of a synthase phosphatase reaction inhibited by ATP-Mg in a liver glycogen particle preparation were complex. In the presence of a physiological concentration of ATP-Mg, synthase phosphatase activity in the glycogen particle follows a biphasic course. Initially, the reaction was inhibited but later the reaction rate accelerated. The reaction was inhibited but the rate was constant in the presence of ATP-Mg with the addition of a physiological concentration of glucose 6-phosphate (Glc 6-P). Therefore, in most subsequent experiments Glc 6-P was added. The concentration of ATP-Mg at which 50% maximal inhibition (I0.5) occurred was approximately 0.1 mM in preparations obtained from rats given glucagon prior to being killed. In preparations from animals given glucose, the I0.5 was increased to 2.0 mM. The maximum inhibition was little changed in preparations from glucose- or glucagon-treated animals. Thus, administration of glucose in vivo reduced the sensitivity of the synthase phosphatase to ATP-Mg inhibition. Complexes of ATP with paramagnetic ions such as Co2+ and Mn2+ were less inhibitory than complexes with diamagnetic ions, including Ca2+ and Mg2+. Magnesium complexes of adenosine tetraphosphate and 5'-adenylimidodiphosphate also were inhibitory. Inhibition was independent of phosphorylase a and not a nonspecific, polyvalent anion effect. The best explanation for the distinctive effects of ATP-Mg in preparations from glucagon- and glucose-treated animals is that the respective treatments promote and stabilize different forms of synthase D or possibly synthase phosphatase with different affinities for ATP-Mg. These forms are interconvertible, as previously suggested, in studies employing EDTA (20).
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PMID:Regulation of liver glycogen synthase phosphatase activity by ATP-Mg. 301 21

We have augmented our previous studies [Storey, Shears, Kirk & Michell (1984) Nature (London) 312, 374-376] on the subcellular location and properties of Ins(1,4,5)P3 (inositol 1,4,5-trisphosphate) phosphatases in rat liver and human erythrocytes. We also investigate Ins(1,3,4)P3 (inositol 1,3,4-trisphosphate) metabolism by rat liver. Membrane-bound and cytosolic Ins(1,4,5)P3 phosphatases both attack the 5-phosphate. The membrane-bound enzyme is located on the inner face of the plasma membrane, and there is little or no activity associated with Golgi apparatus. Cytosolic Ins(1,4,5)P3 5-phosphatase (Mr 77,000) was separated by gel filtration from Ins(1,4)P2 (inositol 1,4-bisphosphate) and inositol 1-phosphate phosphatases (Mr 54,000). Ins(1,4,5)P3 5-phosphatase activity in hepatocytes was unaffected by treatment of the cells with insulin, vasopressin, glucagon or dibutyryl cyclic AMP. Ins(1,4,5)P3 5-phosphatase activity in cell homogenates was unaffected by changes in [Ca2+] from 0.1 to 2 microM. After centrifugation of a liver homogenate at 100,000 g, Ins(1,3,4)P3 phosphatase activity was largely confined to the supernatant. The sum of the activities in the supernatant and the pellet exceeded that in the original homogenate. When these fractions were recombined, Ins(1,3,4)P3 phosphatase activity was restored to that observed in unfractionated homogenate. Ins(1,3,4)P3 was produced from Ins(1,3,4,5)P4 (inositol 1,3,4,5-tetrakisphosphate) and was metabolized to a novel InsP2 that was the 3,4-isomer. Ins(1,3,4)P3 phosphatase activity was not changed by 50 mM-Li+ or 0.07 mM-Ins(1,4)P2 alone, but when added together these agents inhibited Ins(1,3,4)P3 metabolism. In Li+-treated and vasopressin-stimulated hepatocytes, Ins(1,4)P2 may reach concentrations sufficient to inhibit Ins(1,3,4)P3 metabolism, with little effect on Ins(1,4,5)P3 hydrolysis.
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PMID:Dephosphorylation of myo-inositol 1,4,5-trisphosphate and myo-inositol 1,3,4-triphosphate. 303 88


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