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 nifedipine and nicardipine on glucagon-stimulated gluconeogenesis from lactate were examined in primary cultures of rat hepatocytes. Nifedipine and nicardipine (10(-7)-10(-5) M) significantly potentiated the glucagon-stimulated gluconeogenesis from lactate by increasing intracellular cAMP levels. In contrast, diltiazem and verapamil did not potentiate the glucagon-stimulated gluconeogenesis. 1-Methyl-3-isobutylxanthine and papaverine also potentiated the glucagon-stimulated gluconeogenesis from lactate. On the basis of these results, possible mechanisms by which nifedipine and nicardipine potentiate the glucagon-stimulated gluconeogenesis will be discussed.
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PMID:Effects of nifedipine and nicardipine on glucagon-stimulated gluconeogenesis in primary cultures of rat hepatocytes. 133 89

Although it is well known that calcium channel blockers can influence contraction of vascular smooth muscle, there is less knowledge on its effect on excitation contraction coupling in the endocrine glands and more specifically on insulin and glucagon release. In this study, nifedipine was administered in doses of 40 to 80 mg/day to 14 patients with essential hypertension, and its hemodynamic effects were evaluated by non-invasive methods, and its effect on glucose metabolism by an arginine infusion test. Nifedipine produced a significant reduction in systolic and diastolic blood pressure, both after the first dose (30/12 mm Hg) and after 8 weeks of administration (19/12 mm Hg). There were no significant changes in cardiac output (5.1 to 4.9 L/min), muscle (2.4 to 3.2 mL/sec/min) or cutaneous basal flow (9.8 to 8.6 mL/100 mL) as measured non-invasively by echocardiogram and by plethysmography. Insulin and glucagon release were evaluated by the arginine infusion test. Nifedipine produced a tendency toward an increase in glucagon release and a reduction in insulin release although these changes did not reach statistical significance. In this group of patients, nifedipine produced a significant reduction in systolic and diastolic pressure, but no significant changes in insulin or glucagon plasma levels.
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PMID:Hemodynamic and endocrine effects of acute and chronic administration of nifedipine. 265 87

Although it is well known that calcium channel blockers can influence contraction of vascular smooth muscle, there is less knowledge on its effect on excitation contraction coupling in the endocrine glands and more specifically on insulin and glucagon release. In this study, nifedipine was administered in doses of 40 to 80 mg/day to 14 patients with essential hypertension, and its hemodynamic effects were evaluated by non-invasive methods, and its effect on glucose metabolism by an arginine infusion test. Nifedipine produced a significant reduction in systolic and diastolic blood pressure, both after the first dose (30/12 mm Hg) and after 8 weeks of administration (19/12 mm Hg). There were no significant changes in cardiac output (5.1 to 4.9 L/min), muscle (2.4 to 3.2 mL/sec/min) or cutaneous basal flow (9.8 to 8.6 mL/100 mL) as measured non-invasively by echocardiogram and by plethysmography. Insulin and glucagon release were evaluated by the arginine infusion test. Nifedipine produced a tendency towards an increase in glucagon release and a reduction in insulin release although these changes did not reach statistical significance. In this group of patients, nifedipine produced a significant reduction in systolic and diastolic pressure, but no significant changes in insulin or glucagon plasma levels.
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PMID:Hemodynamic and endocrine effects of acute and chronic administration of nifedipine. 265 99

The effect of nifedipine, a calcium antagonist on fasting blood glucose level, glucose tolerance, glucose-induced insulin and glucagon secretion was studied in healthy nondiabetic volunteers. Nifedipine 10mg twice daily for four weeks did not affect fasting blood glucose level, glucose tolerance, glucose-induced insulin and glucagon secretion.
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PMID:Nifedipine and blood glucose in normal human volunteers. 280 80

The aim of this study was to assess whether the potent calcium antagonist nifedipine was capable of modifying the hormonal response to graded exercise in 7 healthy young men. After fasting overnight, each subject came to the laboratory on 2 consecutive mornings. On one day he was given 10 mg of nifedipine sublingually and on the other an identical placebo capsule; the order was randomised in a double-blind fashion over the 2 days. Thereafter each subject performed 2 successive short treadmill runs, equivalent to 60 and 100%, respectively, of maximal aerobic power. While significantly blunting the rise in mean systolic blood pressure and inducing a greater fall in diastolic blood pressure during and after exercise compared with the placebo, nifedipine did not impair the brisk response to pituitary-adrenal hormones (ACTH, cortisol and total catecholamines). Nifedipine also did not modify the effects of short-term exercise in raising mean plasma glucose levels, stimulating pancreatic glucagon secretion and producing a delayed increase in plasma insulin concentrations. Nor did the drug blunt the significant rise of growth hormone and prolactin levels occurring during and after the treadmill run. It was concluded that, apart from inducing significant changes in blood pressure, a single dose of nifedipine does not appear to suppress the counterregulatory hormonal responses to short-term physical activity in healthy men.
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PMID:Nifedipine does not impair the hormonal responses to graded exercise in healthy subjects. 298

In a randomised, double-blind, cross over trial, 25 patients with mild to moderate primary hypertension were given nifedipine 20-40 mg twice daily and labetalol 200-400 mg twice daily after a 4 week period on placebo, followed by the two drugs in combination. The BP during placebo therapy was 164/108 mmHg supine and 159/110 mmHg standing. After monotherapy with nifedipine for 6 weeks the supine BP was reduced by 18/13 mmHg and the standing BP by 20/12 mmHg; with labetalol the corresponding figures were 26/15 mmHg and 28/21 mmHg, respectively. The combined therapy induced a larger fall in BP, by 36/22 mmHg supine and by 39/24 mmHg standing; in 21 of 23 patients the BP became normal. The heart rate (HR) decreased during labetalol treatment alone and on the combined therapy. With nifedipine alone, the HR was unchanged in the supine position and increased on standing. Nifedipine increased plasma renin activity (PRA) and urinary aldosterone excretion (uA), whereas labetalol reduced both. During combination therapy, PRA and uA remained unchanged. There was a slight fall in HDL-cholesterol during treatment with labetalol alone and in combination with nifedipine. The fasting blood glucose increased slightly during treatment with each of the drugs, but neither caused a change in the concentrations of glycosylated haemoglobin A1, serum insulin, C-peptide, or plasma glucagon. Adverse effects as a rule were well tolerated and were related to the pharmacological effects of the drugs. Only 2 patients left the trial, both during labetalol treatment.
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PMID:Antihypertensive and metabolic effects of nifedipine and labetalol alone and in combination in primary hypertension. 390 21

To study the effects of two Ca antagonists, nifedipine and niludipine, on insulin and glucagon secretion, experiments were performed using an in situ local circulation of the canine pancreas. The test drugs were injected into the pancreatic artery in three graded doses (5, 10 and 100 nmoles/kg) during arginine infusion, and blood samples were taken from the pancreatic vein. Verapamil, 10, 100 and 1,000 nmoles/kg, administered in the same way, was used as a control drug. Nifedipine, 5 to 100 nmoles/kg, decreased plasma insulin (IRI) and increased plasma glucagon (IRG) in the pancreatic vein, but caused no marked changes of blood glucose levels in five dogs. Niludipine, 5 to 100 nmoles/kg, injected into the pancreatic artery of 5 dogs, did not change blood glucose levels, but decreased slightly plasma IRI in the pancreatic vein and increased plasma IRG. Verapamil administered to 5 dogs caused no remarkable change of blood glucose or plasma IRG but decreased plasma IRI slightly. The maximum secretion of insulin was significantly lowered by nifedipine and niludipine, and that of pancreatic glucagon markedly increased by niludipine. The experiments revealed that Ca antagonists inhibit insulin secretion, and increase glucagon, and proved that calcium plays an important role in the A cell function of the pancreas.
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PMID:Effects of Ca antagonists, nifedipine, niludipine and verapamil, on endocrine function of the pancreas. 635 51

Nifedipine is a prototypical dihydropyridine calcium channel "blocker" that can cause hypotension and cardiac conduction abnormalities. When compared to other calcium channel antagonists, overdoses have been reported to be relatively benign with treatment consisting mainly of supportive care. We report two pediatric cases of death secondary to accidental ingestion of long acting nifedipine (Adalat). Both cases did not respond to aggressive supportive care that included calcium, atropine, epinephrine, glucagon, sodium bicarbonate, and transthoracic pacing.
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PMID:Fatal nifedipine ingestions in children. 1107 31

Calcium channel blockers (CCB) and beta-blockers (BB) account for approximately 40% of cardiovascular drug exposures reported to the American Association of Poison Centers. However, these drugs represent >65% of deaths from cardiovascular medications. Yet, caring for patients poisoned with these medications can be extremely difficult. Severely poisoned patients may have profound bradycardia and hypotension that is refractory to standard medications used for circulatory support.Calcium plays a pivotal role in cardiovascular function. The flow of calcium across cell membranes is necessary for cardiac automaticity, conduction and contraction, as well as maintenance of vascular tone. Through differing mechanisms, CCB and BB interfere with calcium fluxes across cell membranes. CCB directly block calcium flow through L-type calcium channels found in the heart, vasculature and pancreas, whereas BB decrease calcium flow by modifying the channels via second messenger systems. Interruption of calcium fluxes leads to decreased intracellular calcium producing cardiovascular dysfunction that, in the most severe situations, results in cardiovascular collapse.Although, CCB and BB have different mechanisms of action, their physiological and toxic effects are similar. However, differences exist between these drug classes and between drugs in each class. Diltiazem and especially verapamil tend to produce the most hypotension, bradycardia, conduction disturbances and deaths of the CCB. Nifedipine and other dihydropyridines are generally less lethal and tend to produce sinus tachycardia instead of bradycardia with fewer conduction disturbances.BB have a wider array of properties influencing their toxicity compared with CCB. BB possessing membrane stabilising activity are associated with the largest proportion of fatalities from BB overdose. Sotalol overdoses, in addition to bradycardia and hypotension, can cause torsade de pointes. Although BB and CCB poisoning can present in a similar fashion with hypotension and bradycardia, CCB toxicity is often associated with significant hyperglycaemia and acidosis because of complex metabolic derangements related to these medications. Despite differences, treatment of poisoning is nearly identical for BB and CCB, with some additional considerations given to specific BB. Initial management of critically ill patients consists of supporting airway, breathing and circulation. However, maintenance of adequate circulation in poisoned patients often requires a multitude of simultaneous therapies including intravenous fluids, vasopressors, calcium, glucagon, phosphodiesterase inhibitors, high-dose insulin, a relatively new therapy, and mechanical devices. This article provides a detailed review of the pharmacology, pathophysiology, clinical presentation and treatment strategies for CCB and BB overdoses.
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PMID:Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. 1589 28

Hyperinsulinemic hypoglycemia (HH) is the commonest cause of persistent hypoglycemia in the neonatal and infancy periods. Mutations in the ABCC8 and KCNJ11 genes, which encode subunits of the ATP-sensitive potassium channel in the pancreatic beta cell, are identified in approximately 50% of these patients. The first-line drug in the treatment of HH is diazoxide. Octreotide and glucagon can be used in patients who show no response to diazoxide. Nifedipine, a calcium-channel blocker, has been shown to be an effective treatment in a small number of patients with diazoxide-unresponsive HH. We report a HH patient with a homozygous ABCC8 mutation (p.W1339X) who underwent a near-total pancreatectomy at 2 months of age due to a lack of response to diazoxide and octreotide treatment. Severe hypoglycemic attacks continued following surgery, while the patient was being treated with octreotide. These attacks resolved when nifedipine was introduced. Whilst our patient responded well to nifedipine, the dosage could not be increased to 0.75 mg/kg/day due to development of hypotension, a reported side effect of this drug. Currently, our patient, now aged 4 years, is receiving a combination of nifedipine and octreotide treatment. He is under good control and shows no side effects. In conclusion, nifedipine treatment can be started in patients with HH who show a poor response to diazoxide and octreotide treatment.
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PMID:A combination of nifedipine and octreotide treatment in an hyperinsulinemic hypoglycemic infant. 2493 7


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