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)

Mastoparan, a tetradecapeptide purified from wasp venom, stimulates insulin and glucagon release by rat pancreatic islets in a dose-related manner. In perifusion experiments, mastoparan produces monophasic hormone release, which ceases within 10 min of removal of the peptide. After exposure of the isles to mastoparan, glucose-induced insulin release is clearly retained. In incubation experiments, mastoparan-induced insulin release is greatly blocked by pretreatment of the islets with pertussis toxin or neomycin (inhibitor of phosphoinositide turnover) or by lowering the ambient temperature to 17 C. Pretreatment of the islets with nifedipine (calcium channel blocker), H-7 (inhibitor of A- and C-kinase), somatostatin, or divalent cation-free medium does not affect the response to mastoparan. Pretreatment with parabromophenacylbromide (phospholipase-A2 inhibitor) does not block the response induced by a high concentration of (58 microM) mastoparan. The peptide does not stimulate insulin synthesis during 30 min of incubation. Mastoparan raises the cytosolic free Ca2+ concentration, measured by fura-2, in isolated islet cells at normal (1.9 mM) and very low (6.5 microM) extracellular Ca2+ concentrations. Intravenous administration of mastoparan in rats causes a significant elevation of both insulin and glucagon. Together with the previous data, we conclude that mastoparan stimulates islet hormone release through a temperature-dependent process mediated by pertussis toxin-sensitive GTP-binding protein(s). Activation of phospholipase-C and liberation of intracellular Ca2+ are likely to be coupled to exocytosis. Ca2+ influx through the Ca2+ channel and protein kinase-A and -C appear not to be involved in mastoparan's hormone-releasing action. Phospholipase-A2 may be involved in the hormone release induced by low, but not high, concentrations of the peptide.
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PMID:Mastoparan-induced hormone release from rat pancreatic islets. 172 98

The relationship between stimulation of single C-cells (rMTC-6-23 cell line) with extracellular calcium, glucagon or 8-bromo-cAMP and fluctuations of intracellular free calcium concentration was studied. After pretreatment of rMTC cells with either 1 microM glucagon (30-60 min) or 1 mM 8-bromo-cAMP (5 min) [Ca2+]i started to oscillate when extracellular calcium was raised to 3 mM. These fluctuations in [Ca2+]i could be stopped by chelating the external calcium with EGTA or by adding calcium channel blockers. The voltage-dependent calcium channels in the plasma membrane seem to play a major role in maintaining the oscillations of [Ca2+]i.
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PMID:Rhythmic oscillations of cytosolic free calcium in rat C-cells. 255 59

This study describes functional characteristics of receptors for vasoactive intestinal peptide (VIP) on human Ewing's sarcoma WE-68 cells. These characteristics include 125I-VIP binding capacity, cellular cAMP generation, glycogen hydrolysis, and pharmacological specificity. Binding studies with 125I-VIP showed specific, saturable, binding sites for VIP in WE-68 cells. Scatchard analysis revealed the presence of a single class of high-affinity binding sites that exhibited a dissociation constant (Kd) of 90 pM and a maximal binding capacity (Bmax) of 24 fmol/mg of protein. VIP and VIP-related peptides competed for 125I-VIP binding in the following order of potency: human (h) VIP greater than human peptide with N-terminal histidine and C-terminal methionine (PHM) greater than chicken secretin much greater than porcine secretin. Glucagon and the C-terminal fragments VIP[10-28] and VIP[16-28] and the VIP analogue (D-Phe2)VIP did not inhibit 125I-VIP binding. Addition of hVIP to WE-68 cells provoked marked stimulation of cAMP accumulation, hVIP stimulated increases in cAMP content were rapid, concentration-dependent, and potentiated by 3-isobutyl-l-methylxanthine (IBMX). Half-maximal stimulation (EC50) occurred at 150 nM hVIP. The ability of hVIP and analogues to stimulate cAMP generation paralleled their potencies in displacing 125I-VIP binding. (D-Phe2)VIP, VIP[10-28], VIP[16-28], and (p-Cl-D-Phe6, Leu17)VIP, a putative VIP receptor antagonist, affected neither basal cAMP levels nor hVIP-induced cAMP accumulation. WE-68 cell responses to hVIP were desensitized by prior exposure to hVIP. Desensitization to hVIP did not modify the cAMP response to beta-adrenergic stimulation, and beta-adrenergic agonist desensitization did not modify responses to hVIP. hVIP also induced a time- and concentration-dependent hydrolysis of 3H-glycogen newly formed from 3H-glucose in WE-68 cultures. hVIP maximally decreased 3H-glycogen content by 36% with an EC50 value of about 8 nM. The order of potency of structurally related peptides of hVIP for stimulation of glycogenolysis correlated with their order of potency for inhibition of 125I-VIP binding. IBMX potentiated the glycogenolytic action of hVIP and PHM. The simultaneous presence of the calcium channel antagonist verapamil or the calcium ionophore A 23187 did not influence the glycogenolytic and cAMP stimulatory effects of hVIP. Collectively, these data indicate that Ewing's sarcoma (WE-68) cells are endowed with genuine VIP receptors which are coupled to the formation of cAMP that probably serves a second messenger role in stimulating glycogen hydrolysis in these cells in response to VIP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Vasoactive intestinal peptide receptor regulation of cAMP accumulation and glycogen hydrolysis in the human Ewing's sarcoma cell line WE-68. 256 12

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

This case report describes a 60-year-old diabetic patient whose daily insulin requirements increased by 30 percent following nifedipine administration. Glucagon and intravenous glucose tolerance tests were performed with and without nifedipine treatment, in order to evaluate the roles of decreased pancreatic beta islet cell function and augmented insulin peripheral resistance in the diabetogenic effect of nifedipine. Insulin and calculated glucose peripheral utilization extrapolated from the glucose concentration curves were not significantly different. C-peptide levels tended to be lower with nifedipine treatment at baseline and during the glucagon tests. This may suggest that the altered glycemic control associated with nifedipine was mediated by a suppressed islet beta cell function. The effect of calcium channel-blockers upon glycemic control and the possible mechanisms involved are discussed.
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PMID:Diabetogenic effect of nifedipine. 271 3

The potential correlations between phosphorylase kinase subunit phosphorylation and activation have been examined using 32P-perfused rat hearts exposed to a variety of hormonal stimuli. Phosphate incorporation was measured after isolation of the enzyme by immunoprecipitation from heart extracts. Time courses of catecholamine or glucagon treatment produced a rapid rise in both the activity and the beta subunit phosphorylation of the enzyme, and a slightly slower increase in alpha' subunit phosphorylation. For short durations of catecholamine stimulation, the ratio of phosphate in the alpha' versus beta subunit was dependent upon hormone dose. After removal of hormone, both inactivation and alpha' subunit dephosphorylation were fairly slow, while the beta subunit was dephosphorylated more rapidly. For all of the above conditions, activation correlated with both alpha' and beta subunit phosphorylation. The maximum level of phosphate incorporation observed in response to hormonal stimulation is estimated to be approximately 1.3-1.7 mol of [32P]phosphate/mol of (alpha' beta gamma delta)4, divided about equally between the alpha' and beta subunits. When hearts were treated with hormone either in the absence of added calcium or in the presence of a calcium channel blocker, the time courses of subunit phosphorylation and activation were similar to those seen with standard perfusion conditions, suggesting that if any Ca2+-dependent autophosphorylation of phosphorylase kinase were occurring it does not make a major contribution to the observed hormonal responses. The complicated relationships observed here between phosphorylase kinase subunit phosphorylation and activation for the most part provide physiological affirmation of the patterns observed in vitro, but they also show some possible differences of potential interest.
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PMID:Subunit phosphorylation and activation of phosphorylase kinase in perfused rat hearts. 302 4

Verapamil and diltiazem, calcium channel blockers, inhibited significantly the glucagon-induced glucose output and 45Ca efflux from perfused rat liver at concentrations higher than 50 microM when the perfusate contained calcium. Although the blockers partially interfered with glucagon-induced elevation of cyclic AMP in the tissue, they also inhibited the effects of cyclic AMP. The blockers did not show the inhibitory effects in the absence of perfusate calcium. However, the inhibition of calcium influx into hepatocytes by omission of extracellular calcium or addition of EGTA did not interfere with these effects of glucagon and cyclic AMP. In the presence of extracellular calcium, the blockers did not inhibit cyanide-induced glucose output, indicating that the activity of glycogen phosphorylase and later processes leading to glucose output were not affected by the blockers. These data suggest that, in the presence of calcium, the blockers inhibit the effect of glucagon also at a step (or steps) subsequent to cyclic AMP production and before the activation of phosphorylase b, probably by inhibiting glucagon-induced mobilization of calcium from intracellular calcium pools rather than inhibiting calcium influx into hepatocytes.
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PMID:Inhibition by calcium channel blockers of the glycogenolytic effect of glucagon in perfused rat liver. 628 Apr 34

Historically, the sodium ion has been given prominence in relation to cardiovascular disease, perhaps to the exclusion of other ions. Recently, other ions, including chloride, potassium, magnesium and calcium have received increasing attention in relation to hypertension, cardiac arrhythmias, and metabolic derangements. Endocrine factors controlling these ions have also received increasing attention; they include classic hormonal actions as well as neurotransmission and paracrine hormonal actions. Studies indicate that control of the renin-angiotensin-aldosterone system resides in cytosolic calcium ion levels in the juxtaglomerular cell, as well as chloride ion and prostaglandins at the macula densa. Renin release is stimulated by hyperpolarisation of the juxtaglomerular cell induced by beta 1-agonists, parathyroid hormone, glucagon, magnesium and low cytosol calcium. Renin release is inhibited by high calcium, potassium and angiotensin II. Subsequent to renin release, hormonal regulation includes stimulation of converting enzyme activity by cortisol and prostaglandin (PGE2). Other hormonal control includes antidiuretic hormone producing dilution of extracellular electrolytes and augmented peripheral resistance. A recently identified natriuretic factor isolated from cardiac atria appears to be a potent diuretic with actions similar to that of frusemide (furosemide). Other electrolytes have received closer scrutiny. Chloride may play a dominant role in renal sodium reabsorption, responding to prostaglandin levels. Calcium has been recognised as a basic regulator of the secretion of such hormones as noradrenaline, renin, and aldosterone. As well, calcium ion changes are the means by which smooth muscle contraction is effected. Parathyroid hormone and vitamin D regulate the level of this ion in the body. In addition, a high dietary calcium intake appears to play a protective role against hypertension, while calcium channel blockers appear to reduce blood pressure. Endocrine systems play a major role in the protection against acute elevations in serum potassium by means of insulin action and adrenergic modulation of extrarenal potassium disposal. Aldosterone is recognised as the delayed regulator of potassium excretion. Magnesium levels fall in hyperaldosteronism, hyperparathyroidism, and diabetic keto-acidosis, as well as in malnutrition states. A coexisting potassium deficiency may be refractory to therapy until hypomagnesaemia is corrected. The integrated action of these hormones and electrolytes are thus of major importance in regulation of the cardiovascular system.
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PMID:Endocrine physiology of electrolyte metabolism. 638 78

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.
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PMID:Massive overdose of sustained-release verapamil: a case report and review of literature. 750 8


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