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 effects of two calcium channel blockers, nifedipine and nicardipine, on glucagon-stimulated glycogenolysis in primary cultures of rat hepatocytes were examined in vitro. When nifedipine and nicardipine (10(-7)-10(-6) M) were added to the incubation mixture with various concentrations of glucagon (10(-10)-10(-6) M), these dihydropyridine calcium channel blockers significantly potentiated the glycogenolytic action of glucagon by increasing intracellular cAMP levels. 1-Methyl-3-isobutylxanthine (IBMX), caffeine and papaverine, which is known to inhibit cAMP phosphodiesterase, also potentiated the stimulatory effect of glucagon on the glycogenolysis in a dose-dependent manner. Parallel to the potentiation of glycogenolysis, IBMX also increased the glucagon-stimulated intracellular cAMP levels in a dose-dependent manner. These results suggest that the mechanism of potentiation of the glucagon-stimulated glycogenolysis by nifedipine and nicardipine is related to the known inhibition of cAMP phosphodiesterase by these agents.
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PMID:Nifedipine and nicardipine potentiate glucagon-stimulated glycogenolysis in primary cultures of rat hepatocytes. 750 85

Although poisoning with calcium channel blocking agents is frequent, to our knowledge no cases involving amlodipine have been published. We describe here a case of amlodipine intoxication, in which protracted hypotension did not respond to vasopressor therapy alone. After the addition of continuous calcium chloride and glucagon infusion, blood pressure was restored and vasopressor therapy could be tapered off substantially. When calcium and glucagon were interrupted because of severe hypercalcemia and hyperglycemia, the patient developed irreversible hypotension and died. Either glucagon or calcium or both, and to some extent vasopressors, seem to have constituted effective treatment of hypotension in this case.
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PMID:Fatal intoxication with amlodipine. 776 Apr 51

Obstructive lung disease is a major cause of morbidity and mortality in the United States, and the mortality rate is rising. Successful treatment of acute exacerbations begins with appropriate assessment and intervention. Supplemental oxygen is appropriate for all patients with hypoxemia, and mechanical ventilation should be considered in those with clouded consciousness, profound acidosis, or severe hypoxemia. Inhaled beta 2 agonists are the first line of therapy in acute exacerbations. Anticholinergics, methylxanthines, and corticosteroids may also be useful. Alternative therapies (eg, magnesium, glucagon, calcium channel blockers, clonidine, helium) are receiving increased attention and are undergoing investigation.
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PMID:Acute exacerbations of obstructive lung disease. What to do when immediate care is crucial. 791 Dec 36

The concentration of extracellular calcium rightly regulates calcitonin secretion by calcium influx through dihydropyridine-sensitive voltage-dependent calcium channels; the result is an increase in intracellular calcium. There also exists a cAMP-dependent pathway of calcitonin release activated by glucagon or growth hormone releasing hormone. In thyroid C-cells, as in all cells, there is dual regulation of adenylate cyclase, mediated by inhibitory or stimulatory G proteins; glucagon stimulated cAMP production can be inhibited by somatostatin via pertussis toxin sensitive inhibitory G proteins. Somatostatin inhibits not only cAMP dependent but also calcium-dependent calcitonin secretion. Furthermore, somatostatin inhibits voltage dependent calcium channel currents thereby lowering cytosolic calcium. These actions also involve a pertussis toxin-sensitive inhibitory G protein but they occur independently of changes in the cytosolic cAMP concentration. Thus multiple interactions between second messenger systems at different cellular levels modulate calcitonin secretion.
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PMID:Regulation of calcitonin secretion in vitro. 822

Poisonings due to ingestion of a calcium channel or beta-adrenergic blocker have been the subject of several previous reports, but reports of poisoning due to combined ingestion of these drugs are infrequent. This is a report of suicidal ingestion of nifedipine 600 mg, metoprolol 200 mg, and etizolam 20 mg. Intravenous dopamine, norepinephrine, and calcium chloride had little effect but the administration of methylprednisolone and glucagon were associated with an increase in systolic blood pressure above 100 mm Hg.
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PMID:Poisoning caused by the combined ingestion of nifedipine and metoprolol. 825 3

Glucagon-producing pancreatic islet cells generate calcium-dependent action potentials. By the control of calcium influx through voltage-gated calcium channels, calcium is a tightly regulated second messenger in these cells. It is unknown whether calcium is a signal for glucagon gene transcription. Therefore, rat glucagon reporter fusion genes were transiently transfected into pancreatic islet cell lines. High potassium-induced membrane depolarization activated glucagon gene transcription. The effects of a calcium chelator, calcium channel blockers, calmodulin antagonists, and an inhibitor of calcium/calmodulin-dependent protein kinase II (CaM kinase II) indicate that depolarization-induced glucagon gene transcription depends on calcium influx and CaM kinase II. The depolarization-responsive element was mapped to the glucagon cAMP-responsive element (CRE). The CRE-binding protein CREB was shown, by using GAL4-CREB fusion proteins, to function as a depolarization-regulated transcription factor in pancreatic islet cells. Membrane depolarization and cAMP had synergistic effects on glucagon gene transcription. These results suggest that rat glucagon gene transcription is regulated by membrane electrical activity and calcium influx in pancreatic islet cells. This signal may be transmitted via CaM kinase II and CREB to the glucagon CRE.
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PMID:Membrane depolarization and calcium influx induce glucagon gene transcription in pancreatic islet cells through the cyclic AMP-responsive element. 838 30

The postulated incretin factor glucagon-like peptide-1 (GLP-1) causes a glucose-dependent increase in insulin secretion from perifused rat islets. In the presence of 6 mM glucose the response to 10 nM GLP-1 is characterized by a large initial spike of secretion, followed by a brief, slowly rising phase. However, after 30-40 min of stimulation, this phase subsides to prestimulatory secretory rates. Raising the glucose level to 8 mM, however, amplifies and sustains the stimulatory effect of 10 nM GLP-1. The response to GLP-1 (10 nM) in the presence of 8 mM glucose is abolished by the metabolic inhibitor mannoheptulose (15 mM), and reduced by the calcium channel antagonist nitrendipine (5 microM), or the protein kinase C inhibitor of staurosporine (20 nM). A significant synergistic effect of GLP-1 (10 nM) and 10 microM carbachol, a cholinergic agonist, on insulin secretion was observed in the presence of 6 mM glucose. In the presence of either 6 or 8 mM glucose, GLP-1 (10 nM) has no significant effect on glucose usage or on inositol phosphate generation in [3H]inositol prelabeled islets. The results support the concept that GLP-1 may function as an important physiologic incretin factor, particularly when accompanied by agonists that activate phosphoinositide hydrolysis.
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PMID:Influence of glucagon-like peptide-1 on beta cell responsiveness. 848 20

Hypotension resulting from calcium channel blocker ingestion often is refractory to standard therapeutic modalities. Amrinone and glucagon have been used separately and in combination with other agents in the treatment of calcium channel blocker overdose. We report the successful use of both amrinone and glucagon in the treatment of a 30-year-old woman who ingested 3.6 g of verapamil and presented with refractory hypotension. The use of the two agents together may provide improved inotropic support with minimal increases in myocardial oxygen consumption. In this case, the combination of amrinone and glucagon was safe and effective in the management of the hemodynamic instability associated with calcium channel blocker overdose.
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PMID:Use of amrinone and glucagon in a case of calcium channel blocker overdose. 851 79

The hypotension and myocardial depression that result from calcium channel blocker ingestion often are refractory to standard therapeutic modalities. Anecdotal reports on the use of glucagon have failed to show significant hemodynamic improvement. We report the first case of calcium channel blocker overdose that responded to glucagon. We conclude that glucagon is safe and effective in the management of hemodynamic instability associated with calcium channel blocker poisonings.
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PMID:The use of glucagon in a case of calcium channel blocker overdose. 851 80

Glucagon relieves calcium channel blocker-induced hypotension in animal studies. There are no published case reports of glucagon relieving hypotension in patients with calcium channel blocker poisoning. We describe a patient who developed hypotension after ingestion of 900 mg nifedipine. Therapy with IV lactated Ringer's solution and calcium chloride alone did not relieve his hypotension. However, hypotension rapidly resolved after the addition of IV glucagon therapy. This is the first case report of glucagon therapy at least temporally associated with relief of hypotension in a patient with calcium channel blocker poisoning. More research is needed to determine the appropriate role for glucagon in treating patients with calcium channel blocker poisoning.
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PMID:Amelioration of nifedipine poisoning associated with glucagon therapy. 851 81


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