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. Rat hearts were perfused with 32Pi, and contractile force was increased by positive inotropic agents (agents that increase contractility). The inhibitory subunit of troponin (troponin I) was then isolated by affinity chromatography in 8M-urea, and its 32P content measured. Incorporation of phosphate into the subunit was calculated on the basis of the [gamma-32P]ATP specific radioactivity in the hearts. 2. When hearts were perfused with 30 nM-DL-isoprenaline (N-isopropylnoradrenaline), there was an increase in contractile force over 30s which was paralleled by an increase in troponin I phosphorylation. When hearts were perfused for 25s with increasing concentrations of isoprenaline from 1 NM to 0.6 muM, there was again a parallel increase in contractile force and troponin I phosphorylation. The maximum phosphorylation observed was 1.5 mol of phosphate/mol of troponin I, which was reached after 25s with 0.1 muM-isoprenaline. 3. Hearts were stimulated with a 15s pulse perfusion of 30nM-DL-isoprenaline. There was an increase in contractile force which was followed by a return to the control value within 50s. Troponin I phosphorylation increased to a plateau value which was reached within 30s, and remained constant for 60s after the isoprenaline pulse. Phosphorylase a and 3':5'-cyclic AMP concentration showed changes similar to that of the contractile force. There was no change in 3':5'-cyclic GMP concentration. 4. When hearts stimulated with a 15S pulse of isoprenaline were subsequently perfused with 0.6 muM-acetylcholine, the changes in contractile force, phosphorylase a and 3':5'-cyclic AMP were very similar to those seen with the 15s pulse of isoprenaline alone. Troponin I phosphorylation increased to a maximum 30s after the end of the isoprenaline pulse, but then rapidly decreased during the subsequent 30s. This decrease was preceded by a 60% increase in the concentration of 3':5'-cyclic GMP. 5. Hearts were perfused with 0.2 muM-glucagon for periods up to 60s. Contractile force showed little change for the first 30s, but then increased rapidly. This was paralleled by changes in 3':5'-cyclic AMP concentration. Troponin I phosphorylation increased slowly, but the increase in contractile force had reached a maximum before significant phosphorylation had occurred. 6. It is concluded that under certain conditions, e.g. immediately after beta-adrenergic stimulation, there is a good correlation between contractile force and troponin I phosphorylation. However, under other conditions, e.g. when contractile force is decreasing after removal of beta-adrenergic stimulation or in the presence of glucagon, contractile force and troponin I phosphorylation are not well correlated. These results suggest that mechanisms for modifying cardiac contractility, other than troponin I phosphorylation, must be present in rat heart.
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PMID:Studies on the phosphorylation of the inhibitory subunit of troponin during modification of contraction in perfused rat heart. 18 17

We have investigated the respective roles of insulin and glucagon in the initiation of hepatic glycogen degradation during the early postnatal period in rats, with special regard on the inhibitory effect of insulin on this process. Pregnant rats were rendered either slightly (8.5 mM) or highly hyperglycemic (22 mM) by infusing glucose during the last week of pregnancy. Fasted, newborn rats were studied from delivery to 16 h postpartum. At birth, newborns from slightly hyperglycemic rats showed higher glycemia and insulinemia and lower plasma glucagonemia compared with controls. Newborns from highly hyperglycemic rats were still more hyperglycemic and exhibited low plasma glucagon concentrations, but they were not hyperinsulinemic. In control newborns, hepatic glycogen breakdown was triggered by 2 h after delivery. By contrast, hyperglycemic-hyperinsulinemic newborns (newborns from slightly hyperglycemic rats) were unable to mobilize liver glycogen before 8-10 h after delivery. In hyperglycemic-normoinsulinemic newborns (newborns from highly hyperglycemic rats), hepatic glycogen concentration significantly started to decline 2 h after delivery and was no longer different from controls at 8 h. Anti-insulin serum injection at delivery promoted a prompt decrease in liver glycogen stores in controls as well as in newborns from slightly hyperglycemic rats. Phosphorylase a/synthase a ratio rose rapidly after delivery in controls and in newborns from highly hyperglycemic rats (maximum 4 h), whereas in newborns from slightly hyperglycemic rats, it rose much more slowly than in the two other groups (maximum 16 h). These data suggest that, in newborns from hyperglycemic mothers, hyperinsulinemia during late fetal and early neonatal life is the main factor preventing postnatal hepatic glycogenolysis.
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PMID:Impaired hepatic glycogenolysis related to hyperinsulinemia in newborns from hyperglycemic pregnant rats. 228 64

Phosphorylase a activity was measured in hepatocytes from fed rats, some of which received ip chlorpropamide injections for 5 days preceding death (20 mg/100 g BW X day for 5 days). Chlorpropamide treatment significantly depressed basal phosphorylase a activity and lessened the increments in the activity of this enzyme induced by 10(-10) -10(-8) M glucagon and arginine vasopressin. The reductions in phosphorylase a activity after treatment with chlorpropamide were more than sufficient to explain the accompanying decreases in hepatic glucose production. Since glucagon and arginine vasopressin stimulate alternate pathways of phosphorylase activation and since chlorpropamide antagonizes both hormones, it is likely that the drug acts at or distal to the intracellular site (phosphorylase kinase) at which the two activation pathways converge.
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PMID:Inhibition of hormonal activation of hepatic phosphorylase by chlorpropamide: evidence for an intracellular site of drug action. 396 24

In in vitro cultures of liver from Ambystoma mexicanum glycogenolysis was stimulated by adrenaline, glucagon, and vasopressin in a dose-dependent manner. Maximum activity was seen at 10(-6) M hormone while 10(-9) M was without effect. Dibutyryl cyclic AMP (10(-3) M) stimulated glycogenolysis maximally although 10(-5) M had no effect. The glucose release brought about by adrenaline was blocked by the beta-adrenergic antagonist propranolol but not by prazosin or yohimbine which are alpha 1- and alpha 2-adrenergic antagonists. Cyclic AMP concentrations in liver were elevated within 1 min of administration of adrenaline and remained elevated for at least 60 min. Phosphorylase a activity was elevated 10 min after addition of adrenaline and remained elevated for at least 6 hr. The rise in hepatic cyclic AMP concentration and phosphorylase a activity was largely blocked by propranolol. These findings are consistent with adrenaline acting via a beta-adrenergic receptor in A. mexicanum. Glycogenolysis in A. mexicanum liver was stimulated by isoprenaline and phenylephrine and in each case the stimulation was reduced in the presence of propranolol but unaffected by phentolamine. High concentrations of methoxamine, a specific alpha 1-agonist, had no effect upon glycogenolysis. These findings suggest that alpha-adrenergic receptors play no role in regulation of glycogenolysis in A. mexicanum.
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PMID:Hormonal control of glycogenolysis and the mechanism of action of adrenaline in amphibian liver in vitro. 630 36

Three stages of development of hepatic glycogen metabolism in the rat were studied. These included the last stage of gestation, in which large scale synthesis and accumulation of glycogen takes place, the perinatal period of glycogenolysis, and the suckling period up to and including weaning. The role of insulin in the regulation of the key rate-limiting enzymes of glycogen synthesis (glycogen synthase) and glycogen breakdown (glycogen phosphorylase) was studied as was the role of the key phosphoprotein phosphatase enzymes that regulate activation of synthase (synthase phosphatase) and inactivation of phosphorylase (phosphorylase phosphatase). Glycogen accumulates in significant quantities on days 20-21 of gestation in the rat (term, 22 days). Associated with this increased rate and amount of glycogen accumulation is an increase in glycogen synthase a and synthase phosphatase and phosphorylase phosphatase activities associated with the endoplasmic reticulum (ER). Concomitantly, fetal insulin levels are elevated as is the insulin to glucagon molar ratio and the synthase a/phosphorylase a ratio. At birth, these hepatic glycogen stores are rapidly degraded, and synthase a levels are diminished, as are ER-associated synthase phosphatase and phosphorylase phosphatase activities. Phosphorylase a levels are markedly elevated at this time as well. Insulin levels are decreased, as is the insulin to glucagon molar ratio. Gradually over a period of 4 weeks after birth, glycogen levels increase in the liver, accompanied by increased ER-associated phosphatase activities and an increased insulin to glucagon molar ratio. The data support a role for increased ambient insulin concentrations in regulation of the periods of active glycogen synthesis and accumulation in pre- and postnatal rat liver. A possible site of action of insulin is the ER and associated phosphoprotein phosphatase activities.
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PMID:Regulation of hepatic glycogen metabolism in pre- and postnatal rats. 640 92

Rats fed ad libitum were given insulin alone (4 U/kg), glucagon alone (25 micrograms/kg), or insulin and glucagon sequentially. Phosphorylase a and synthase R activities, hepatic glycogen, uridine diphosphoglucose, inorganic phosphate (Pi), and plasma glucose, lactate, glucagon, and insulin concentrations were determined over the subsequent 40 min. In separate animals, muscle extraction of 2-deoxy-D-[3H]glucose also was determined. After glucagon administration, glycogen phosphorylase a and plasma glucose were increased within 5 min. However, the glycogen concentration did not decrease for 20 min. Glucagon administration to rats pretreated with insulin stimulated a similar increase in phosphorylase a activity. Again, glycogen was not degraded for 20 min. After insulin only, glycogen concentration remained unchanged. Plasma glucose decreased as expected. In each group, muscle extraction of 2-deoxy-D-[3H]glucose increased compared with the controls (P < 0.05). In summary, glucagon and/or insulin administration did not stimulate significant glycogen degradation for 20 min, even though phosphorylase was activated. The mechanism remains to be determined.
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PMID:Effects of glucagon with or without insulin administration on liver glycogen metabolism. 914 96