Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study we examine the hypothesis that an inositol glycan phosphate can act similarly to insulin on intact cells. The inositol glycan phosphate used in this study (glycan alpha) was isolated previously from the glycoinositol phospholipid anchor of human erythrocyte acetylcholinesterase and was shown to have the structure glycine-ethanolamine-PO4-Man-Man-(N,N-dimethylethanolamine-PO4)Man- (N,N-dimethyl)GlcN-inositol-PO4. The cellular response investigated was the glucagon-stimulated activation of glycogen phosphorylase in rat hepatocytes. When hepatocytes were incubated with 20 nM glucagon for 4 min, the ratio of phosphorylase a activity to total phosphorylase increased from a basal value of 0.49 +/- 0.02 to 0.82 +/- 0.03 (mean +/- SE, n = 15). Inclusion of either 100 nM insulin or 3-10 microM glycan alpha during the glucagon incubation significantly decreased the glucagon-stimulated activity ratio to 0.74 +/- 0.03 for either agent. Furthermore, hepatocyte preparations differed in their response to insulin and were divided into insulin-responsive and -resistant groups. Glycan alpha had a significant effect only in the insulin-responsive group for which the observed activity ratio for 10 microM glycan alpha plus glucagon (0.68 +/- 0.05) compared closely with that for insulin plus glucagon (0.70 +/- 0.04). For the insulin-resistant group, the activity ratio in the presence of 10 microM glycan alpha was 0.81 +/- 0.03, unchanged from the control with glucagon alone. Because glycan alpha contains an inositol phosphate group, the effect of inositol cyclic 1,2-phosphate on the glucagon-stimulated activity ratio was determined.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inositol glycan phosphate derived from human erythrocyte acetylcholinesterase glycolipid anchor and inositol cyclic 1,2-phosphate antagonize glucagon activation of glycogen phosphorylase. 834 43

Rats were infused with endotoxin (50 micrograms/100 g body wt) for 3 h, and the parenchymal cells of the liver were maintained in primary culture for 1-3 h. The effects of vasopressin, norepinephrine, and glucagon on the activation of phosphatidylinositol (PI)-phospholipase C, phosphatidylcholine (PC)-phospholipase D, and glycogen phosphorylase a were investigated. Activation of PI-phospholipase C was markedly reduced, particularly with norepinephrine. This confirms that one of the early metabolic impairments seen in acute endotoxin treatment is inhibition of PI-phospholipase C activity. However, the ability of vasopressin, norepinephrine, and glucagon to stimulate glycogen phosphorylase a and PC-phospholipase D was not affected by this endotoxin treatment. We conclude that activation of phosphorylase a by vasopressin and norepinephrine is not entirely dependent on the activation of PI-phospholipase C and inositol trisphosphate formation.
 ...
PMID:LPS inhibits PI-phospholipase C but not PC-phospholipase D or phosphorylase activation by vasopressin and norepinephrine. 838 92

1. In rat liver cells micromolar concentrations of adenosine 5'-[beta-thio]diphosphate (ADP beta S), activate glycogen phosphorylase by an adenosine 3':5'-cyclic monophosphate (cyclic AMP)- independent mechanism. 2. As with adenosine 5'-triphosphate (ATP), ADP beta S also inhibits the rise in cyclic AMP after glucagon. 3. Cytosolic Ca2+ measured in single cells is rapidly increased with a pattern similar for ADP beta S and for ATP. 4. At variance with ATP, ADP beta S hardly increases inositol 1,4,5-trisphosphate (IP3) levels. 5. Phorbol myristic acetate, which inhibits only slightly the glycogenolytic effect of ATP, almost completely abolishes this effect of ADP beta S. 6. With adenosine 5'-[beta-[35S]thio]diphosphate (ADP beta[35S]) as radioligand, we detected specific purinoceptors on rat liver plasma membranes. Binding consists of a major binding component with KD = 0.7 microM and Bmax = 51 pmol mg-1 of protein, probably mediating the activation of glycogen phosphorylase, and a minor high affinity, low capacity binding component with no obvious function. 7. It is concluded that the differences in biological effects between ATP and ADP beta S may involve different receptors and/or different transduction mechanisms and that ADP beta[35S] can be used to detect the specific binding sites for ADP beta S.
 ...
PMID:Characterization of the effects of adenosine 5'-[beta-thio]-diphosphate in rat liver. 838 33

Hepatocytes from chronically endotoxemic rats, or appropriate saline controls, were maintained in primary culture for 3 or 20 h. The ability of a variety of hormones to stimulate glycogen phosphorylase a was examined. At 3 h in culture, hepatocytes from endotoxemic rats had lower basal activities and exhibited impaired response to vasopressin, angiotensin II, and, to a lesser extent, norepinephrine and glucagon. The norepinephrine response was predominantly of the alpha-type in the saline rats but mixed alpha- and beta-type in the endotoxic cells. After 20 h in culture, vasopressin and angiotensin II responses were still impaired, while norepinephrine and glucagon responses were similar to those seen in the saline cells. The response to norepinephrine was predominantly of the beta-type in the endotoxic cells but still of the alpha-type in the saline cells. The results show that multiple mechanisms are involved in endotoxin-mediated inhibition of glycogen phosphorylase a activity and that alterations in intracellular calcium homeostasis play more of a significant role than adenosine 3',5'-cyclic monophosphate-mediated processes in diminished responsiveness of the liver seen in endotoxemia.
 ...
PMID:Shift from alpha- to beta-type adrenergic receptor-mediated responses in chronically endotoxemic rats. 838 59

Hepatocytes were isolated from human liver tissue by a two-step perfusion technique. They were treated with vasopressin, angiotensin, ATP and phenylephrine, which are known to be Ca(2+)-mediated glycogenolytic agents in rat liver tissue, and as a control, they were treated with the cyclic AMP-mediated hormones glucagon and isoproterenol. All agonists induce a time-dependent activation of glycogen phosphorylase. Glucagon and isoproterenol induce a somewhat higher degree of phosphorylase activation compared with vasopressin, angiotensin, ATP and phenylephrine, which all increase inositol tris-phosphate levels and have no effect on the cyclic AMP levels. The total activity of glycogen phosphorylase (a + b), amounting to 30 to 35 mU/mg protein, is found to be much lower than that found in rat liver tissue. Because only minor differences could be found, we conclude that the regulation of glycogen phosphorylase in human liver tissue is basically the same as that found in rat liver tissue.
 ...
PMID:Regulation of glycogen phosphorylase activity in isolated human hepatocytes. 838 94

Glycogen biosynthesis involves a specific initiation event, mediated by a specialized protein, glycogenin. Glycogenin undergoes self-glucosylation to generate an oligosaccharide primer, which, when long enough, supports the action of glycogen synthase to elongate the polysaccharide chain, leading ultimately to the formation of glycogen. We report that primed glycogenin is also a substrate for glycogen phosphorylase. Phosphorylase removed glucose from the oligosaccharide attached to glycogenin in a phosphorolysis reaction that required phosphate and produced glucose 1-phosphate. The phosphorylated form, phosphorylase a, was much more effective than the dephosphorylated phosphorylase b. However, in the presence of the allosteric effector AMP, phosphorylase b also catalyzed the phosphorolysis reaction. Glucose, an allosteric inhibitor of phosphorylase, inhibited the reaction. Glycogen, but not a short oligosaccharide (maltopentaose), also inhibited the reaction. Treatment of fully primed glycogenin with phosphorylase converted the glycogenin to a form with slightly lower apparent molecular weight, which was less effective as a substrate for glycogen synthase. These results suggest a novel role for phosphorylase in the control of glycogen biosynthesis. We propose that the glucosylation level of glycogenin would be determined by the balance between the self-glucosylation reaction and the opposing action of phosphorylase. The level of glucosylation would in turn determine whether or not glycogenin was an effective primer for glycogen synthase. In this way, several known controls of phosphorylase activity, such as epinephrine, glucagon, and insulin, could influence not only the elongation/degradation stage of glycogen metabolism but also its initiation.
 ...
PMID:Initiation of glycogen synthesis. Control of glycogenin by glycogen phosphorylase. 840 25

The rate of glycogenolysis was measured using 13C-NMR in vivo in the rat heart following a glucagon bolus. Glycogen that had just been synthesized during a 50 min infusion of D-[1-13C]glucose and insulin was degraded at a rate of 2.5 mumol/min/g wet wt following a 250 micrograms bolus of glucagon. If a second 50 min infusion of unlabelled glucose followed the D-[-13C]glucose, the rate of mobilization of the labelled glycogen following glucagon was slower (0.52 mumol/min/g wet wt), indicating that the labeled glycogen was less accessible to the activated phosphorylase. Glycogen phosphorylase a (GPa) activity was measured in hearts freeze-clamped at intervals after the glucagon bolus. Activity rose rapidly to 6-fold basal and then returned to basal over 20-30 min (t1/2 decay of phosphorylase activity = 5.1 min). This time course paralleled the exponential fall in heart glycogen which followed glucagon (t1/2 = 4.3 min). Throughout the post-glucagon period the activity of phosphorylase exceeded the rate of glycogenolysis. These findings suggest that the activity of the phosphorylated form of glycogen phosphorylase (GPa) is an important but not the sole determinant of glycogen breakdown in the heart after a glucagon bolus.
 ...
PMID:The time course of myocardial glycogenolysis stimulated by glucagon. 847 25

1. ATP exerts multiple receptor-mediated effects on isolated hepatocytes: glycogenolysis through the activation of glycogen phosphorylase (cAMP-independent, IP3/calcium-mediated), inactivation of glycogen synthase, inhibition of the glucagon effect on cAMP, activation of phospholipase D. The fact that some of these effects can be selectively altered and that they are not, or differently, reproduced by some other analogues of ATP, suggests the presence of more than one receptor. (i) Pertussis toxin abolishes the anti-glucagon effect of ATP without affecting its glycogenolytic effect. (ii) Single cell calcium measurements reveal major differences between ATP and ADP, (iii) 2MeSATP and ADP beta S, in clear contrast to ATP, barely increase the levels of IP3 and their glycogenolytic effects is completely blocked by phorbol ester treatment of hepatocytes. (iv) 2MeSATP differs from ADP beta S since it has no anti-glucagon effect. 2. Effects of UTP on isolated hepatocytes so far do not show any difference with effects of ATP, suggesting interaction with the same receptor(s). 3. It is proposed that liver plasma membranes contain (at least) three different receptors mediating (a) the activation of phospholipase C, (b) the activation of phospholipase D and (c) the inhibition of adenylate cyclase.
 ...
PMID:The complex interaction of ATP and UTP with isolated hepatocytes. How many receptors? 848 12

The present study was designed to investigate the hormonal regulation of rat liver glycogenolysis in growth hormone (GH) deficiency. To this end, hepatocytes were isolated from control, GH-deprived (hypophysectomized and treated with triiodothyronine [T3] and corticotropin), and 7-day GH-supplemented fed rats and incubated with glucagon and alpha 1-adrenergic agonist (phenylephrine) to measure the hormonal activation of both glycogen phosphorylase and glucose production from glycogen stores. GH deficiency induces a combined decrease of 50% of the glycogen content, the activity of glucose-6-phosphatase, and the maximal hormone-induced glycogen phosphorylase activity. Daily GH injections restore the levels of both glycogen phosphorylase and glucose-6-phosphatase. These enzymatic inductions occur without normalization of insulinemia. Despite the reduced levels of key enzymes of glycogenolysis, the stimulation of glucose production from glycogen in response to glucagon and phenylephrine is not modified in GH-deprived rats. An increase in the intrinsic activity of one or both of the enzymatic steps is postulated to compensate for the lower levels of enzymes, as indicated by the slopes of the correlation between glucose production and phosphorylase a activity (107 and 216 nmol glucose produced/min/U phosphorylase a [P < .001] in control and GH-deprived rats, respectively). GH replacement enhances maximal phosphorylase activity and brings the correlation toward the control value (slope, 128 nmol glucose produced/min/U phosphorylase a). Our findings demonstrate that glycogenolysis in hepatocytes isolated from GH-deprived rats is normal, despite a reduction of glycogen phosphorylase and glucose-6-phosphatase activities.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of growth hormone deficiency on hormonal control of hepatic glycogenolysis in hypophysectomized rat. 849 19

The perivenous and periportal zones of the liver acinus differ in enzyme complements and capacities for gluconeogenesis, glycolysis and other metabolic processes. The biochemical factors governing this metabolic zonation are still poorly understood. Glucagon-mediated protein phosphorylation is an important factor in the regulation of hepatic metabolism. Here we show, by comparing the 32P-labelling pattern of isolated periportal and perivenous hepatocytes, that glucagon promotes the phosphorylation of zone-specific peptides as well as three common peptides (glycogen phosphorylase, glycogen synthase and pyruvate kinase) in the two cell types. We propose that the zone-specific phosphorylation of peptides is an important factor governing the shortterm zonation of metabolic processes in the liver.
 ...
PMID:Glucagon stimulates phosphorylation of different peptides in isolated periportal and perivenous hepatocytes. 854 72


<< Previous 1 2 3 4 5 6 7 8 9 10