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 effect of the adenosine A1 receptor activation on calcitonin secretion was studied in medullary thyroid carcinoma cells of the rat (rMTC 6-23). Calcitonin was determined by radioimmunoassay, intracellular cAMP by protein binding assay, intracellular calcium in fura-2 loaded single cells using microspectrofluorimetry, and calcium channel activity by patch clamp technique. The adenosine A1 receptor analogue N-6 phenylisopropyl-adenosine (PIA) (10(-10)-10(-6) M) inhibits dose-dependently glucagon (10(-7) M) and rGRH (10(-7) M) stimulated cAMP formation and calcitonin secretion. These effects were partly abolished by pretreatment with pertussis toxin (PT) (100 ng/ml). PIA (10(-10)-10(-6) M) also suppressed extracellular calcium-stimulated calcitonin secretion, rises in intracellular calcium, and calcium channel currents. PT (100 ng/ml) pretreatment again partly abolished this inhibitory effect. The addition to the medium of adenosine deaminase (0.4 U/ml) stimulated calcitonin secretion. Our results suggest that in calcitonin-secreting cells A1 receptors couple to adenylate cyclase and calcium channels via PT-sensitive G proteins and thus inhibit calcitonin secretion. Adenosine seems to act as an autocrine/paracrine factor in calcitonin-secreting cells.
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PMID:Adenosine A1-receptors inhibit cAMP and Ca2+ mediated calcitonin secretion in C-cells. 855 39

A preterm female infant presented with intractable hypoglycaemia within 10 minutes of delivery. Normoglycaemia could be maintained only by the intravenous infusion of glucose at a rate of 20-22 mg/kg/min. Persistent hyperinsulinaemic hypoglycaemia of infancy was diagnosed from an inappropriately raised plasma insulin concentration (33 mU/l) at the time of hypoglycaemia (blood glucose < 0.5 mmol/l). Medical treatment with glucagon, somatostatin, and diazoxide led to only a modest reduction in the intravenous glucose requirement; a 95% pancreatectomy was performed and histological 'nesidioblastosis' confirmed. In vitro electrophysiological studies using patch clamp techniques on isolated pancreatic beta cells characterised the ionic basis for insulin secretion in nesidioblastosis. The beta cells were depolarised in low ambient glucose concentrations with persistently firing action potentials; these were blocked reversibly by the calcium channel blocking agent verapamil. Persistent postoperative hyperinsulinaemic hypoglycaemia was treated with oral nifedipine. This increased median blood glucose concentrations from 3.5 to 4.8 mmol/l and increased in duration the child's tolerance to fasting from 3 to 10.5 hours. These data allude to an abnormality in the ionic control of insulin release in nesidioblastosis and offer a new logical approach to treatment which requires further evaluation.
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PMID:Ionic control of beta cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade. 866 50

Recent experiments indicate that the calcium store (e.g., endoplasmic reticulum) is involved in electrical bursting and [Ca2+]i oscillation in bursting neuronal cells. In this paper, we formulate a mathematical model for bursting neurons, which includes Ca2+ in the intracellular Ca2+ stores and a voltage-independent calcium channel (VICC). This VICC is activated by a depletion of Ca2+ concentration in the store, [Ca2+]cs. In this model, [Ca2+]cs oscillates slowly, and this slow dynamic in turn gives rise to electrical bursting. The newly formulated model thus is radically different from existing models of bursting excitable cells, whose mechanism owes its origin to the ion channels in the plasma membrane and the [Ca2+]i dynamics. In addition, this model is capable of providing answers to some puzzling phenomena, which the previous models could not (e.g., why cAMP, glucagon, and caffeine have ability to change the burst periodicity). Using mag-fura-2 fluorescent dyes, it would be interesting to verify the prediction of the model that (1) [Ca2+]cs oscillates in bursting neurons such as Aplysia neuron and (2) the neurotransmitters and hormones that affect the adenylate cyclase pathway can influence this oscillation.
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PMID:Modeling slowly bursting neurons via calcium store and voltage-independent calcium current. 869 30

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.
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PMID:The effects of amrinone and glucagon on verapamil-induced myocardial depression in a rat isolated heart model. 918 18

Blood-borne insulin is known to cross the blood-brain barrier (BBB) where it can act as a satiety peptide. We examined in mice the pharmacokinetics and characteristics of such passage by multiple-time regression analysis. The unidirectional influx constant (Ki) of human insulin radioactively labeled with iodine (I-Ins) ranged from 0.87 to 1.7 microliters/g-min. The transport of I-Ins was inhibited almost 50% by 0.1 micrograms/mouse of unlabeled human insulin, a dose that had no effect on serum glucose. Similar results were found with rat insulin. The results with self-inhibition suggest that any hemoencephalic signal transmitted by the blood to brain transport of insulin is independent of the effects of insulin on glucose. The transport of I-Ins was altered by aluminum but not by administration of tyrosine, verapamil, or leptin, indicating independence from amino acid transport, the p-glycoprotein system, a slow calcium channel, or leptin transport. By contrast with insulin, enzyme degradation limited the uptake and accumulation by brain of intravenously injected, radioactively labeled glucagon and glucagon-like peptide. In conclusion, these results are consistent with the view that insulin can affect satiety and related behaviors independently of its peripheral effects by crossing the BBB to act within the brain.
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PMID:Transport of insulin across the blood-brain barrier: saturability at euglycemic doses of insulin. 939 46

Glucagon has been used to treat the hypotension associated with calcium channel antagonist poisoning in adult patients. We describe the successful use of glucagon in a pediatric patient poisoned with nifedipine and clonidine whose hypotension was unresponsive to fluid resuscitation, calcium chloride, and dopamine.
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PMID:The use of glucagon in nifedipine poisoning complicated by clonidine ingestion. 943 7

Nine cases of symptomatic bradycardia are presented in which treatment with intravenous glucagon was administered when atropine failed to improve the patient's condition significantly. Although the cause often was not obvious at presentation, all nine subjects took oral medications that could have contributed to the development of symptomatic bradycardia. Eight of nine patients demonstrated clinical improvement 5 to 10 min after glucagon administration, which was consistent with its peak clinical action. Beta-blockers, calcium channel blockers, and digoxin were ultimately thought to have contributed to the majority of these presentations. This report suggests that glucagon may have a role in the treatment of symptomatic bradycardia, particularly in the presence of beta-adrenergic blockade and perhaps calcium channel blockade. Furthermore, the results in these cases suggest that future clinical trials should not be limited to drug-induced symptomatic bradycardia.
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PMID:A potential role for glucagon in the treatment of drug-induced symptomatic bradycardia. 967 88

Amlodipine is a relatively new agent that has the longest half-life of all calcium channel blockers. This report describes a severe overdose that resulted in prolonged and severe hemodynamic compromise for up to 10 days, but responded to aggressive therapy with calcium, glucagon, and other vasoactive medicines.
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PMID:Amlodipine overdose causes prolonged calcium channel blocker toxicity. 972 75

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

Alcoholic hepatitis is a multisystem disease seen in individuals who chronically abuse alcohol. When severe, it is associated with a very high mortality rate, with nearly 50% of severely affected persons dying within 1 month of hospitalization. Primary therapy is complete alcohol abstinence and supportive care. Corticosteroids have been shown to be beneficial in a subset of severely ill patients with alcoholic hepatitis and concomitant hepatic encephalopathy. Pentoxifylline has been shown to improve short-term survival rates. Other pharmacologic interventions, including colchicine, propylthiouracil, calcium channel antagonists, and insulin with glucagon infusions, have not been proven to be beneficial. Nutritional supplementation with high-calorie, high-protein diets does not improve mortality rates. Orthotopic liver transplantation is highly controversial in this population of patients and currently is not indicated as definitive treatment. Extracorporeal liver support devices are still in their developmental stage and are only experimental.
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PMID:Alcoholic Hepatitis. 1169 77


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