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 hyperglycemic response of adult male Wistar rats given dieldrin (63 mg/kg, po) and either phenobarbital (40 mg/kg, ip), atropine (4 mg/kg, sc), L-alpha-methyldopa (200 mg/kg, ip), or DL-propranolol (8 mg/kg, sc) was studied. The hyperglycemia was maximal (73% above control values) 2 hr after exposure to dieldrin alone. Phenobarbital reduced the hyperglycemia by 41% and abolished dieldrin-induced convulsions. It also prevented the increases that dieldrin causes in hepatic phosphoenolpyruvate carboxykinase (PEPCK) activity. These results suggest that the dieldrin-induced hyperglycemia is mediated via the CNS. Atropine prevented the hyperglycemia for 2 hr and delayed the attainment of maximal glucose concentrations for another 2 hr. However, additional atropine 4, 8, 12, and 18 hr after the dieldrin had no effect. Atropine also increased (125%) the time to the onset of dieldrin-induced convulsions. It did not alter hepatic PEPCK activity. L-alpha-Methyldopa decreased (24%) the hyperglycemic response in the first 2 hr after dieldrin treatment. It caused similar reductions in blood glucose when given during the peak hyperglycemic response. L-alpha-Methyldopa also reduced (49%) the dieldrin-effected increase in hepatic PEPCK activity. DL-Propranolol did not alter the effects of dieldrin. Thus these data suggest that the dieldrin-induced hyperglycemia is mediated by the CNS, primarily via enhanced cholinergic activity and secondarily by increased alpha-adrenergic activity. It is suggested that the pancreas responds to the cholinergic outflow by increasing the secretion of glucagon while simultaneously responding to the alpha-adrenergic outflow by decreasing insulin secretion.
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PMID:The effects of phenobarbital, atropine, L-alpha-methyldopa, and DL-propranolol on dieldrin-induced hyperglycemia in the adult rat. 404 84

The effects of 2-deoxy-D-glucose (2-DG) on plasma levels of somatostatin-like immunoreactivity (SLI) were examined in conscious normal dogs. After an iv infusion of 2-DG (400 mg/kg . h for 15 min), plasma SLI rose significantly from a mean baseline of 130 +/- 5 pg/ml (mean +/- SEM) to a mean peak of 204 +/- 25 pg/ml (P less than 0.005) at 25 min. Plasma insulin and glucagon also increased significantly. Atropine (200 microgram/kg . h for 35 min, iv) and hexamethonium (5 mg/kg, iv) markedly suppressed the SLI response to 2-DG, suggesting that it might be mediated, at least in part, by the autonomic nervous system. In contrast, the plasma insulin and plasma glucagon responses to this glucose analog were only slightly affected by atropine or hexamethonium pretreatment. Carbachol (0.2 mg, sc) caused a mean maximal increase in SLI of 43 +/- 14% (P less than 0.005) and atropine (200 micrograms/kg . h, iv) caused a mean maximal decrease of 25 +/- 2% (P less than 0.001) from the respective baseline levels. Plasma insulin and glucagon rose promptly after carbachol and were unchanged by atropine. To assess th contribution of 2-DG-stimulated gastric acid secretion in the 2-DG-induced SLI rise 2-DG was infused during the infusion of the H2-receptor antagonist cimetidine (3.0 mg/kg . h). Plasma SLI, nevertheless, increased significantly from a mean baseline of 112 +/- 6 pg/ml to a mean peak of 158 +/- 19 pg/ml (P less than 0.005) at 20 min, although the magnitude of the response was substantially reduced (P = NS). These observations suggest that in the conscious dog, 2-DG stimulates SLI secretion in part via cholinergic mechanism.
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PMID:Effect of 2-deoxy-D-glucose on plasma somatostatin levels in conscious dogs. 611 May 37

The glucose dependent glucagon and insulin responses to electrical vagal stimulation in anesthetized splanchnicotomized young pigs were studied after administration of various pharmacological blocking agents. Hexamethonium completely abolished the responses, regardless of the glucose level. Atropine was without effect on the glucagon as well as the insulin response, regardless of stimulation frequency, glucose level, or dose of atropine. Neither propranolol nor a combination of propranolol and phenoxybenzamine inhibited the response. Our findings indicate that neither adrenergic fibres nor fibres impinging on muscarinic cholinergic receptors are involved in the pancreatic endocrine response to vagal stimulation.
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PMID:Nervous control of pancreatic endocrine secretion in pigs. II. The effect of pharmacological blocking agents on the response to vagal stimulation. 611 94

Two cases of severe beta-blocker overdose are presented that were treated successfully with glucagon therapy. The effects of glucagon in reversing the cardiovascular depression of profound beta-blockade, including its mechanism of action, onset and duration of action, dosage and administration, cost and availability, and side effects are reviewed. Medical complications of beta-blocker overdose include hypotension, bradycardia, heart failure, impaired atrioventricular conduction, bronchospasm and, occasionally, seizures. Atropine and isoproterenol have been inconsistent in reversing the bradycardia and hypotension of beta-blocker overdose. Glucagon increases heart rate and myocardial contractility, and improves atrioventricular conduction. These effects are unchanged by the presence of beta-receptor blocking drugs. This suggests that glucagon's mechanism of action may bypass the beta-adrenergic receptor site. Because it may bypass the beta-receptor site, glucagon can be considered as an alternative therapy for profound beta-blocker intoxications. The doses of glucagon required to reverse severe beta-blockade are 50 micrograms/kg iv loading dose, followed by a continuous infusion of 1-15 mg/h, titrated to patient response. Glucagon-treated patients should be monitored for side effects of nausea, vomiting, hypokalemia, and hyperglycemia. The high cost and limited availability of glucagon may be the only factors precluding its future clinical acceptance.
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PMID:Glucagon therapy for beta-blocker overdose. 614 98

Effects of cholinergic mechanisms on glucagon and epinephrine responses to insulin-induced hypoglycemia were examined in diabetic and age-matched control male rats. Atropine did not affect plasma glucose levels or plasma glucagon concentrations, in the basal state, in normal or short-term diabetic rats (10 to 15 days following streptozotocin injection). However, atropine blocked the glucagon response to insulin hypoglycemia in both normal and short-term diabetic rats. Subcutaneous injection of carbachol also failed to alter basal plasma glucose, glucagon, or epinephrine values in both normal and diabetic rats. The lack of glucagon and epinephrine responses to insulin hypoglycemia in long-term diabetic rats (80 to 100 days after streptozotocin injection) was reversed with a single dose of carbachol. Carbachol exaggerated the glucagon response to insulin hypoglycemia in normal and short-term diabetic rats. These results demonstrate that the parasympathetic nervus system plays an important role in the glucagon release in response to insulin hypoglycemia in rats. The lack of glucagon response to insulin hypoglycemia observed in long-term diabetic rats could be due to deteriorated parasympathetic nervous system and also could be corrected with carbachol.
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PMID:Role of parasympathetic nervous system in glucagon response to insulin-induced hypoglycemia in normal and diabetic rats. 639 89

Massive overdosage of adrenergic blocking drugs is associated with severe morbidity and a high mortality rate. We report the case of a 24-year-old medical intern who ingested 9.6 g acebutolol, 7.2 g labetalol and 0.625 g trimipramine in an attempted suicide. Blood samples drawn on admission were shown to contain markedly elevated plasma levels of acebutolol and its major metabolite and of labetalol. The patient was deeply comatose on admission. The heart rate was 60 min-1 (sinus rhythm) and the blood pressure was clinically unrecordable. Atropine, isoproterenol and dopamine initially had no effect on either heart rate or blood pressure. Only following the administration of inordinately large doses of isoproterenol and dopamine, together with glucagon was a clinical response obtained. The patient remained haemodynamically dependent on dopamine for 12 h and isoproterenol for 65 h. The total dose of isoproterenol administered was 260 mg, two thirds of this during the first 12 h. The patient left hospital well after 7 days but was readmitted after 26 days because of intestinal obstruction due to ischemic bowel necrosis.
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PMID:Survival following massive overdose of adrenergic blocking agents (acebutolol and labetalol). 661 79

1. The efficacies of some standard preparations of CCK were compared and the effects of some drugs and peptide hormones on the responsiveness of the rabbit isolated gall-bladder to cholecystokinin were studied with an established automatic method of estimating cholecystokinin. 2. Atropine, propranolol, phentolamine mesylate and lignocaine were shown to have no effect on the responsiveness of the rabbit isolated gall-bladder. 3. Glucagon, somatostatin, pentagastrin, pancreatic polypeptide, motilin and the Karolinska preparation of secretin had no effect on the preparation alone and caused only slight changes when given with cholecystokinin. 4. The Boots preparation of secretin exhibited a small cholecystokinin effect when given alone, but considerably inhibited cholecystokinin-induced contractions. 5. The desulphated C-terminal octapeptide of cholecystokinin also exhibited inhibitory effects.
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PMID:Effects of some drugs and peptide hormones on the responsiveness of the rabbit isolated gall-bladder to cholecystokinin. 715 34

Human glucagonoma cells were isolated and maintained in vitro. Incubation experiments showed that carbachol (Cch) induced the simultaneous release of glucagon, VIP (vasoactive intestinal polypeptide), and pancreatic polypeptide (PP) at levels significantly higher than basal levels. Atropine abolished the stimulatory effect of Cch on glucagon, VIP, and PP release. An immunohistological study of the tumor tissues revealed that the cells contained glucagon, VIP, and PP. These findings demonstrate, for the first time, the in vitro release of glucagon from glucagonoma cells by Cch stimulation.
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PMID:Acetylcholine regulates glucagon secretion from human glucagonoma cells. 787 80

1. Insulin sensitivity was quantified using a modified euglycaemic technique after hepatic cholinergic blockade with atropine and compared with that after surgical denervation. 2. Intraportal administration of atropine produced dose-dependent inhibition of insulin sensitivity in glucose metabolism. ED50 of atropine was 0.99 mg kg-1 (1 mg = 1.5 microM) with maximum inhibition of 40.3 +/- 11.6%. 3. Atropine (3 mg kg-1) reduced insulin sensitivity by a similar amount (33.6 +/- 3.4%) to that produced by hepatic surgical denervation (37.8 +/- 9.8%). Doses greater than 3 mg kg-1 failed to further alter the insulin resistance produced by surgical denervation or atropine (3 mg kg-1) administration, suggesting that activation of hepatic parasympathetic nerves is necessary to fully express the insulin effect. 4. Atropine reduced insulin sensitivity without changes in plasma concentrations of glucagon or insulin. The temporal response to insulin in this euglycaemic study was not changed after atropine administration or after surgical hepatic denervation. 5. It is suggested that hepatic parasympathetic nerves show a synergistic effect with insulin. Disease states that result in hepatic parasympathetic neuropathy would be expected to produce an insulin resistant liver. 6. The modified euglycaemic clamp method for assessing insulin responses was shown to be reproducible up to four times in the same animal and was sufficiently sensitive and quantitative to be able to generate a dose-response curve in each animal for atropine-induced insulin resistance.
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PMID:Induction of insulin resistance by cholinergic blockade with atropine in the cat. 874 76

The insulinotropic glucagon-like peptide 1 (GLP-1) originates from the lower intestines. Surprisingly, food ingestion induces a rapid increase of GLP-1 plasma levels. Therefore, a complex regulation for postprandial GLP-1 secretion must exist, which cannot be solely explained by direct contact of nutrients in the gut lumen with the GLP-1-releasing L cells. This was addressed in the present study utilizing an isolated vascularly perfused rat ileum preparation. Cholinergic (methacholine) as well as peptidergic stimulation by glucose-dependent insulin-releasing polypeptide (synonym: gastric inhibitory polypeptide) (GIP) strongly enhanced GLP-1 secretion from the rat ileum. The stimulation of GLP-1 secretion by methacholine was abolished by addition of atropine and partly reduced by galanin. Galanin dose-dependently antagonized the stimulatory effect of GIP on GLP-1 release. Atropine was without effect. Furthermore, employing double immunohistochemistry labeling techniques galanin-immunoreactive nerves were detected in the vicinity of GLP-1-immunostained cells. Our data indicate that stimulatory and inhibitory mediators regulate GLP-1 secretion and that galanin is a likely inhibitor.
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PMID:Galanin is a potent inhibitor of glucagon-like peptide-1 secretion from rat ileum. 880 63


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