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)

Some characteristics of adenylate cyclase of catfish (Ictalurus melas) liver membranes were studied, and the effects of catecholamines and of glucagon were tested. The enzyme has an optimum temperature of 40 degrees C, and a Km for ATP of 0.16 mM at 30 degrees C, and requires Mg2+ for its activity. The enzyme activity is inhibited with a Ca2+ concentration higher than 5 X 10(-5) M, and enhanced with F- higher than 10(-4) M. The response of adenylate cyclase to GTP is biphasic, with a maximum of activity at 10(-5) M GTP. Catecholamines (epinephrine, norepinephrine, isoproterenol, phenylephrine) enhance cyclase activity. Propranolol inhibits the increase in enzyme activity induced by catecholamines, whereas phentolamine is ineffective. This indicates that catecholamines (phenylephrine included) activate adenylate cyclase through a beta-adrenergic mechanism. Glucagon (mammalian) has a smaller effect than epinephrine in increasing the enzyme activity of catfish hepatocyte membranes. This fact is the opposite of that observed for the cyclase activity of rat liver membranes.
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PMID:Adenylate cyclase of catfish hepatocyte membranes: basal properties and sensitivity to catecholamines and glucagon. 285 Sep 55

Alpha adrenergic blockade with phentolamine (10 microM) reduces the glucagon response to severe glucopenia (from 150 to 25 mg/dl) to 22% of the control values in the isolated perfused rat pancreas. Propranolol (10 microM) had no significant effect. Neither alpha nor beta adrenergic blockade reduced the magnitude of glucopenic suppression of insulin secretion, but phentolamine increased insulin levels before and during glucopenia. The pattern of somatostatin secretion in these experiments resembled that of insulin. Depletion of norepinephrine from sympathetic nerve endings by pretreatment with 6-hydroxydopamine lowered the pancreatic norepinephrine content to less than 20% of control values and reduced the glucagon response to glucopenia to 69% of the controls. Combined alpha and beta adrenergic blockade during less severe glucopenia (from 120 to 60 mg/dl) reduced the glucagon response to 21% of controls. However, slight glucopenia (from 100 to 80 mg/dl), which elicited only 11% increase in glucagon in the control experiments, was not altered significantly by combined alpha and beta adrenergic blockade. Morphologic studies of adrenergic nerve terminals labeled with [3H]norepinephrine revealed associations with alpha cells. It is concluded that in the isolated rat pancreas adrenergic mediation accounts for most of the glucagon but not insulin response to glucopenia. It is controlled within the pancreas itself, possibly through a direct enhancement by glucopenia of norepinephrine release from nerve endings.
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PMID:Adrenergically mediated intrapancreatic control of the glucagon response to glucopenia in the isolated rat pancreas. 285 31

In conscious dogs, phentolamine infusion significantly increased fasting portal vein insulin, glucagon, and decreased net hepatic glucose output and plasma glucose. Propranolol significantly decreased portal vein insulin, portal flow, and increased hepatic glucose production and plasma glucose. Phentolamine, propranolol, and combined blockade reduced glucose absorption after oral glucose. alpha, beta, and combined blockade abolished the augmented fractional hepatic insulin extraction after oral glucose. Despite different absolute amounts of glucose absorbed and different amounts of insulin reaching the liver, the percent of the absorbed glucose retained by the liver was similar for control and with alpha- or beta blockade, but markedly decreased with combined blockade. Our conclusions are: (a) phentolamine and propranolol effects on basal hepatic glucose production may predominantly reflect their action on insulin and glucagon secretion; (b) after oral glucose, alpha- and beta-blockers separately or combined decrease glucose release into the portal system; (c) net hepatic glucose uptake is predominantly determined by hyperglycemia but can be modulated by insulin and glucagon; (d) direct correlation does not exist between hepatic delivery and uptake of insulin and net hepatic glucose uptake; (e) alterations in oral glucose tolerance due to adrenergic blockers, beyond their effects on glucose absorption, can be, to a large extent, mediated by their effects on insulin and glucagon secretion reflecting both hepatic and peripheral glucose metabolism.
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PMID:Effects of alpha and beta adrenergic blockade on hepatic glucose balance before and after oral glucose. Role of insulin and glucagon. 287 78

The effect of electrical stimulation of the splanchnic and the vagus nerve supply to isolated, perfused pig pancreas on the secretion of insulin, glucagon and pancreatic polypeptide (PP) was investigated. Functional integrity of the autonomic nerve supply was assessed by the effect of nerve stimulation on vascular resistance and exocrine secretion. Splanchnic nerve stimulation increased glucagon and PP output (2 to 3-fold) and inhibited insulin output (by 42%). Propranolol abolished the effect on PP and glucagon secretion, but did not affect the inhibition of insulin secretion. Phenoxybenzamine abolished the inhibition of insulin secretion, reduced the effect on glucagon secretion and enhanced the effect on pancreatic polypeptide secretion. Combined alpha- and beta-adrenergic blockade abolished all effects of splanchnic nerve stimulation. Vagus nerve stimulation increased the secretion of all 3 hormones (PP: up to 30-fold, insulin and glucagon: 3 to 5-fold). The effect on insulin and PP-secretion was mimicked by acetylcholine at 10(-7)-10(-6) M, whereas glucagon secretion was inhibited. The effect of vagus nerve stimulation on insulin and PP secretion was augmented by physostigmine, and inhibited (but not abolished) by atropine at 10(-7)-10(-6) M. The effect on glucagon secretion was inhibited by physostigmine and unaffected by atropine. It is concluded that all of the effects of splanchnic nerve stimulation on insulin and PP secretion can be explained by interactions of norepinephrine with excitatory beta-receptors on PP-cells and inhibitory receptors on the insulin cells. Both cell types are also stimulated via muscarinic cholinoceptors, but the partial atropine resistance suggests that other transmitters participate in vagal activation. The nervous regulation of glucagon secretion is complex and may involve the peptidergic innervation of the pancreatic islets.
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PMID:Autonomic nervous control of the endocrine secretion from the isolated, perfused pig pancreas. 287 20

Using a new in vitro procedure of the isolated perfused rat pancreas with vagal innervation, electrical vagal stimulation produced an increase in both insulin and glucagon secretion in proportion to the pulse frequency, but an inhibition in somatostatin release. When atropine was infused, both insulin and glucagon responses to vagal stimulation were partially suppressed, whereas somatostatin release was enhanced. In the presence of hexamethonium, vagal stimulation failed to affect insulin, glucagon, or somatostatin secretion. Propranolol partially blocked both insulin and glucagon responses but did not influence somatostatin response. Phentolamine had no significant effect on release of hormones. Simultaneous administration of propranolol and phentolamine tended to inhibit both insulin and glucagon responses to vagal stimulation. These findings suggest that not only a cholinergic but also a noncholinergic neuron may be involved in vagal regulation of pancreatic hormone secretion and that these neurons may be under the control of preganglionic vagal fibers via nicotinic receptors.
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PMID:Vagal regulation of insulin, glucagon, and somatostatin secretion in vitro in the rat. 288 48

Early metabolic and endocrine changes in calves in response to two beta-adrenoceptor agonists in the absence and presence of the beta-adrenoceptor blocking agent propranolol have been studied in calves. The agonists were administered p.o. with milk in different amounts, whereas propranolol was infused i.v. for 10 h. Respiration volume, O2 consumption, CO2 production, respiratory quotient, blood glucose, lactate, non-esterified fatty acids and insulin transiently increased within 2-4 h in a dose-dependent manner, whereas glucagon, adrenaline, noradrenaline, triiodothyronine, urea, albumin and protein did not change significantly. Propranolol completely inhibited the effects on glucose, lactate, non-esterified fatty acids and insulin. Six hours after the administration of the beta-adrenoceptor agonists, the glucose clearance rates following i.v. infusion of glucose were markedly reduced and the glucose decrements in response to an i.v. injection of insulin were much smaller than in the absence of the beta-adrenoceptor agonists. The metabolic changes demonstrate an enhanced glycogenolysis and fat mobilisation, an increased metabolic rate and the development of insulin resistance within 6 h after the administration of the beta-adrenoceptor agonists.
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PMID:Early metabolic and endocrine effects of perorally administered beta-adrenoceptor agonists in calves. 290 69

Post-exercise ketosis is not abolished by glucose ingestion immediately after exercise but is counteracted by simultaneous beta-adrenergic blockade. To investigate the effect of beta-adrenergic blockade on post-exercise ketosis without the ingestion of glucose, we administered propranolol (1 mg/kg body mass) to 15 carbohydrate-starved people, of whom five had just walked 9 km in 2 h. There were 43 control subjects (no propranolol). The blood concentration of 3-hydroxybutyrate rose from 0.18 +/- 0.02 (S.E.M.) mmol/l at 07.00 h to 0.35 +/- 0.04 mmol/l at 09.00 h whether the subjects had exercised during those 2 h or not (d.f. = 57). The blood concentration of 3-hydroxybutyrate at 15.00 h in the groups not treated with propranolol was not affected by exercise (0.95 +/- 0.90 mmol/l; d.f. = 42). Propranolol significantly raised the concentration of 3-hydroxybutyrate at 15.00 h to 1.68 +/- 0.26 mmol/l when given after exercise (d.f. = 4), but lowered it to 0.46 +/- 0.07 mmol/l in the non-exercised group (d.f. = 9). This was not accompanied by significant differences in the blood concentrations of glucose, free fatty acid, insulin or glucagon. The difference in response to propranolol administration is probably determined by the alanine and lactate flux from muscle for hepatic oxaloacetate synthesis.
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PMID:beta-Adrenergic blockade counteracts starvational ketosis, but aggravates post-exercise ketosis in non-athletes. 290 99

To determine the mechanism of time-dependent hyperglycemia due to intracranial injection of 2-deoxy-D-glucose (2DG), we examined the effects of various blockers of the autonomic nervous system on the hyperglycemia and hyperglucagonemia induced by intracranial injection of 2DG in male Wistar rats in light and dark periods. Hexamethonium inhibited the hyperglycemia in both light and dark periods but did not block the hyperglucagonemia in either period. Intracranial injection of 2DG did not affect the plasma insulin concentration in saline-treated control rats, but hexamethonium caused an increase in the basal plasma insulin concentration and further increase in the plasma concentration after 2DG injection in the light period. Phenoxybenzamine, an alpha-adrenergic blocker, inhibited the hyperglycemia only in the light period and the hyperglucagonemia only in the dark period and slightly stimulated the basal concentrations of insulin and glucagon only in the light period. Propranolol, a beta-adrenergic blocker, blocked the hyperglycemia and hyperglucagonemia and also lowered the basal plasma glucagon concentration in both periods. Atropine sulfate and atropine methyl nitrate, muscarinic blockers, inhibited hyperglycemia only in the light and dark period, respectively. In contrast, both drugs blocked the hyperglucagonemia in both periods. These findings suggest that the autonomic nervous system is involved time dependently in the hyperglycemia and hyperglucagonemia due to intracranial 2DG injection.
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PMID:Time-dependent involvement of autonomic nervous system in hyperglycemia due to 2-deoxy-D-glucose. 290 68

Propranolol-induced hypoglycemia in hemodialysis patients has been increasingly recognized. We studied the effects of a nonselective beta-blocker (propranolol) and a beta 1-selective-blocker (metoprolol) on glucose metabolism during pharmacologic hyperglucagonemia in these patients. cAMP and insulin responses to glucagon were noted to be significantly higher in all patients after dialysis. This may possibly be due to the removal of a dialyzable factor suppressing these responses. However, despite a similar cAMP response, patients on propranolol had significantly lower glucose response than those not receiving beta-blocker before and after dialysis. While patients on metoprolol also had impaired glucose response before dialysis, this significantly improved after dialysis possibly due to the removal of active metabolite(s). Results suggest that metoprolol has less interference on glucose response to glucagon than propranolol in hemodialysis.
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PMID:Effects of propranolol and metoprolol on glucose, cyclic AMP and insulin responses during pharmacologic hyperglucagonemia in hemodialysis patients. 298 50

The chronic treatment of rats with the beta-adrenergic antagonist propranolol causes a double increase in the amount of beta-adrenergic receptors in the cardiac membranes. The purpose of the paper is to investigate the effect of propranolol on the activity and regulatory properties of rat heart adenylate cyclase. Propranolol injections to rats for 3 weeks (10-20 mg/l kg bw) did not influence the enzyme basal activity but caused a rise of a degree of myocardial adenylate cyclase activation by isoproterenol and glucagon.
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PMID:[Development of cardiac adenylate cyclase hypersensitivity to isoproterenol in the chronic action of propranolol on rats]. 298 93


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