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)

The current study was performed in order to investigate whether verapamil would affect the basal blood glucose concentration in a metabolic state characterized by an increased hepatic gluconeogenesis. For that purpose verapamil (5 mg/h) was infused i.v. during three hours in a group of healthy subjects fasted for 36 h, and for comparison also in healthy subjects fasted overnight. Verapamil was found to lower the basal blood glucose concentration in the 36 h fasted subjects. No effect of verapamil was seen in the overnight-fasted group. Since both the insulin and the glucagon concentrations remained unaffected by verapamil after the 36 h fast, other glucose-regulatory factors must have been responsible for the blood glucose lowering effect of the drug. An effect upon the cytosolic calcium concentration in the hepatocytes causing a decrease in the hepatic gluconeogenesis, is a feasible mechanism by which verapamil might have lowered the blood glucose concentration in the individuals subjected to a prolonged fast.
 ...
PMID:Blood glucose lowering effect of verapamil in fasted man. 639 56

The present investigation was carried out in 16 healthy subjects in order to study whether calcium antagonism would affect the hypoglycemic response to insulin, and/or whether it would affect the insulin and glucose responses to glucagon. For this purpose verapamil, a potent calcium-blocking agent, was used. Verapamil infused alone did not affect the basal insulin or glucose concentrations. However, such infusion reduced the hypoglycemic response to insulin. Furthermore, the glucose response to glucagon was augmented by simultaneous infusion of verapamil, whereas the insulin response to glucagon was unaffected. When healthy volunteers were simultaneously infused with both calcium and verapamil the glucose response to glucagon was no longer augmented. The insulin response to glucagon also remained unaffected. These findings indicate that intravenous verapamil has hyperglycemic effects, unrelated to insulin, under certain conditions. They also imply that exogenous hypercalcemia counteracts the augmentative effect of verapamil on the glucose response to glucagon.
 ...
PMID:Effect of verapamil on glucose response to intravenous injection of glucagon and insulin in healthy subjects. 699 47

The present investigation was designed to evaluate the effect of acute and protracted verapamil administration on insulin and glucagon secretion in man. For this purpose, 14 normal subjects received two consecutive glucose pulses (5 g.i.v. in less than 20 sec or 20 g.i.v. in less than 1 min, 7 subjects for each group), 70 or 90 min apart, before and during an infusion of verapamil (160 microgram/min). Seven additional normal subjects received two consecutive arginine pulses (5 g i.v.), 70 min apart. In 14 inpatients with coronary heart disease, we investigated the effect of protracted verapamil administration. Seven of these subjects underwent two oral glucose tolerance tests (100 g) and the other 7 two arginine tests (30 g) before and after a 10-day treatment with verapamil, 240 mg/die p.o. divided into three doses; the last dose, 80 mg, was given orally 1 h before the performance of the post-treatment test. Verapamil significantly inhibited the acute insulin response (AIR, mean change from 3-10 min) to glucose (5 g), as well as the AIR and AGR (acute glucagon response) to arginine (5 g). By contrast, verapamil failed to alter significantly the AIR to the higher glucose pulse. There was no significant change of oral glucose tolerance after verapamil, nor was there a change in insulin response to oral glucose. By contrast, insulin and glucagon responses to arginine infusion were significantly reduced by the drug.
 ...
PMID:Modulation by verapamil of insulin and glucagon secretion in man. 701 49

The current study was performed in order to investigate whether verapamil would affect the glucose response to glucagon differently in patients with non insulin-dependent diabetes mellitus (NIDDM) compared with age-matched normoglycemic controls. For that purpose glucagon was injected intravenously on a background infusion of verapamil, and for comparison also on a background infusion of saline in these two groups. Verapamil was found to blunt the glucose response to glucagon in the patients with NIDDM, whereas it augmented the glucose response to glucagon in the controls. This discrepancy could not be explained on the basis of verapamil-induced changes in the release of insulin, since verapamil did not effect the serum responses to glucagon. However, it could reflect the differences in hepatic handling of glucose, which has been shown to prevail in patients with NIDDM compared with healthy controls.
 ...
PMID:Calcium-antagonistic effects on glucose response to glucagon in patients with non insulin-dependent diabetes mellitus and in normoglycemic subjects. 703 91

Verapamil 99 is a commonly prescribed medicine for treatment of hypertension, angina, and migraine headache. Toxicity with sustained-release verapamil may be prolonged, and manifest with hypotension, bradycardia, metabolic acidosis, and hyperglycemia. Currently, because of the lack of a specific antidote management of verapamil, toxicity is mainly supportive. Treatment with inotropic support, glucagon, calcium, and cardiac pacing may be effective in some cases. A review of 20 cases and a case report of sustained-release verapamil overdose are described. The authors describe a patient who ingested 24 g of slow-release verapamil. This is the largest overdose of sustained-release verapamil reported in English literature. The patient was managed aggressively with gastric lavage, inotropic support, and continuous infusion of calcium and glucagon. The patient's survival may have been due to the continuous intravenous calcium gluconate and glucagon infusion. Both of these treatment modalities should be considered in patients with moderate to severe calcium channel blocker overdose.
 ...
PMID:Massive overdose of sustained-release verapamil: a case report and review of literature. 750 8

Biliary excretion of reverse triiodothyronine (rT3) was estimated in rats during hypoglycemia induced by a 10-min infusion of 1 U of insulin (INS) and for the following 5 h. During that period an increase in biliary rT3 was found. This was seen also during the infusion of exogenous glucagon (10 micrograms in 1.2 ml of saline per 1 h for 5 h) given independently of INS. The infusion of glucose (1 g/kg per 50 min or 2 g/kg per 110 min) following INS infusion delayed the increase in rT3. The increase in rT3 was prevented by actinomycin D (1 mg/kg) when injected before (90 min), but not after (30 min) INS, and also by cycloheximide (2.5 mg/kg) injected immediately before INS. The same dose of cycloheximide also prevented a similar increase of rT3 during the infusion of exogenous glucagon. Verapamil (5 mg/kg divided into five doses per 4 h) blunted the increase of rT3. These data indicate that following INS injection counter-regulatory hormones may be responsible for the increased production of rT3; this altered metabolic activity apparently is dependent on protein synthesis.
 ...
PMID:Acute changes in biliary excretion of reverse triiodothyronine in rats after insulin-induced hypoglycemia: effect of glucose, verapamil, cycloheximide and actinomycin D. 774 5

The influence of aging on beta-receptor and glucagon-receptor control of glycogenolysis was investigated in rat hepatocytes. The beta-receptor-induced glucose output was detectable only in senescent rats, was partly dependent on extracellular Ca2+, and was inhibited by 4 beta-phorbol 12-myristate 13-acetate (PMA), insulin, and the Ca(2+)-antagonists, verapamil and nifedipine. Chelation of extracellular Ca2+ potentiated the effect of nifedipine only. In contrast, glucagon-stimulated glycogenolysis, similar in mature and senescent rats, was independent on extracellular Ca2+ and was unaffected by PMA. Verapamil, in senescent rats only, and nifedipine, in mature and senescent rats, inhibited glucagon-stimulated glucose output only in the presence of Ca2+. Insulin inhibited glucagon-induced glucose output, irrespective of the age of the rat and the presence of Ca2+. We conclude that the beta-receptor component in the adrenergic regulation of glycogenolysis in senescent rats consists of a major Ca(2+)-independent and a minor Ca(2+)-dependent part, displaying different sensitivity towards protein kinase C (PKC), Ca(2+)-antagonists, and insulin. Aging does not change the capacity of glucagon to induce a full glycogenolytic response in the absence of extracellular Ca2+; Ca(2+)-influx, however, seems to be involved when extracellular Ca2+ is present, and this sensitivity is increased on aging.
 ...
PMID:Influence of aging on the beta- and glucagon-receptor-mediated glycogenolysis in rat hepatocytes. 823 Dec 83

Because of its positive inotropic effects that are independent of cyclic AMP, insulin was compared to epinephrine and glucagon as a novel treatment for cardiac toxicity from verapamil. Twenty-four alpha-chloralose-anesthetized mongrel canines of either sex were instrumented to monitor standard hemodynamic and cardiodynamic parameters and maximum elastance at end systole, via the transit-time technique, as our index of contractility. Toxicity was induced by 0.1 mg/kg/min of verapamil (i.v.), until 50% reduction in mean arterial blood pressure or complete AV dissociation for 30 min. This was followed by continuous infusion of 1.0 mg/kg/hr of verapamil during one of four treatment protocols: 1) control (0.9% NaCl, 2.0 ml/min); 2) epinephrine (1.0 micrograms/kg/min); 3) hyperinsulinemic-euglycemic (HIE) clamp (recombinant insulin at 4.0 U/min with 20% dextrose, arterial glucose clamped); or 4) glucagon (0.2-0.25-mg/kg bolus infusion followed by 150-micrograms/kg/min infusion). Treatments were continued until death or 240 min after which time surviving animals received a 3.0-mg/kg additional bolus of verapamil. Verapamil decreased all hemodynamic parameters during titration. All controls died within 85 min. All treatments tended to improve hemodynamics; however, HIE significantly improved maximum elastance at end systole, left ventricular end diastolic pressure and coronary artery blood flow vs. other treatments (P < .05, repeated measures). Glucagon transiently restored sinus rhythm (four animals), but in all cases reverted to A-V dissociation, coincident with sharp decreases in circumflex artery blood flow and contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine. 824 50

1. We measured the ability of glucagon and amrinone, used alone and in combination, to improve the myocardial function in a rat isolated heart model of calcium channel blocker (CCB) cardiotoxicity. 2. Verapamil 10(-4) mol consistently decreased heart rate and cardiac contractile force in our Langendorff rat isolated heart preparations. Glucagon increased the heart rate in a dose-dependent fashion. Amrinone increased the heart rate only at the 1 x 10(-1) mol concentration, and had no significant effect on cardiac contractility. 3. A positive linear correlation was found between the glucagon concentration and the percent recovery of baseline contractile force. 4. Although complete reversal of verapamil-induced myocardial depression occurred at glucagon concentrations of > 3 x 10(-6) mol, amrinone produced only 23.8 +/- 3.6% recovery from baseline at its highest concentration (4 x 10(-3) mol). 5. When glucagon and amrinone were administered together, there was no additional increase over glucagon alone in the increase in contractile force. 6. Glucagon, and not amrinone, is an appropriate agent, capable of reversing verapamil-induced myocardial toxicity in this rat isolated heart model. In vivo studies should be performed to assess whether this may be a reliable therapy in clinical cases.
 ...
PMID:The effects of amrinone and glucagon on verapamil-induced myocardial depression in a rat isolated heart model. 918 18

Verapamil poisoning is known to produce hyperglycemia and metabolic acidosis in humans. The purpose of this study was to elucidate mechanisms of verapamil-induced hyperglycemia in awake dogs. Mongrel canines were chronically instrumented to permit studies in the conscious state. In six healthy dogs, steady-state glucose infusion requirement after 1 hr of insulin infusion at 1000 mU/min was 19 +/- 1 mg/kg/min. In six separate dogs, verapamil toxicity was induced via verapamil infusion in the portal vein; during verapamil toxicity, the glucose infusion requirement with an insulin infusion rate of 1000 mU/min was significantly decreased (3 +/- 1 mg/kg/min; p < 0.05, unpaired t test). Eleven other verapamil-toxic dogs were also treated with either saline (n = 6, 3.0 ml/kg/hr) or glucagon (n = 5, 10 microg/kg/min). Insulin concentrations were not changed vs basal concentrations in either group. Catecholamine concentrations increased at least 15-fold in all groups (from 458 +/- 169 to 6973 +/- 480 pg/L in the saline-treated group). Glucose concentrations increased in saline-treated animals from 3.7 +/- 0.3 to 11.2 +/- 1.0 micromol/L, and with glucagon treatment, increased from 3.3 +/- 0.3 to 16.1 +/- 1.6 micromol/L (p < 0.05 vs saline, ANOVA). Verapamil poisoning appears to produce hyperglycemia by inducing systemic insulin resistance, blocking insulin release, together with an intact stress hormone response and glucogenic capacity.
 ...
PMID:The diabetogenic effects of acute verapamil poisoning. 926 9


<< Previous 1 2 3 Next >>