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 hyperglycemic response of adult male Wistar rats given dieldrin (63 mg/kg, po) and either phenobarbital (40 mg/kg, ip), atropine (4 mg/kg, sc), L-alpha-methyldopa (200 mg/kg, ip), or DL-propranolol (8 mg/kg, sc) was studied. The hyperglycemia was maximal (73% above control values) 2 hr after exposure to dieldrin alone. Phenobarbital reduced the hyperglycemia by 41% and abolished dieldrin-induced convulsions. It also prevented the increases that dieldrin causes in hepatic phosphoenolpyruvate carboxykinase (PEPCK) activity. These results suggest that the dieldrin-induced hyperglycemia is mediated via the CNS. Atropine prevented the hyperglycemia for 2 hr and delayed the attainment of maximal glucose concentrations for another 2 hr. However, additional atropine 4, 8, 12, and 18 hr after the dieldrin had no effect. Atropine also increased (125%) the time to the onset of dieldrin-induced convulsions. It did not alter hepatic PEPCK activity. L-alpha-Methyldopa decreased (24%) the hyperglycemic response in the first 2 hr after dieldrin treatment. It caused similar reductions in blood glucose when given during the peak hyperglycemic response. L-alpha-Methyldopa also reduced (49%) the dieldrin-effected increase in hepatic PEPCK activity. DL-Propranolol did not alter the effects of dieldrin. Thus these data suggest that the dieldrin-induced hyperglycemia is mediated by the CNS, primarily via enhanced cholinergic activity and secondarily by increased alpha-adrenergic activity. It is suggested that the pancreas responds to the cholinergic outflow by increasing the secretion of glucagon while simultaneously responding to the alpha-adrenergic outflow by decreasing insulin secretion.
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PMID:The effects of phenobarbital, atropine, L-alpha-methyldopa, and DL-propranolol on dieldrin-induced hyperglycemia in the adult rat. 404 84

1. The cardiac actions of amiodarone, a benzofuran derivative used in the treatment of angina pectoris, have been compared with those of (+/-)-propranolol in anaesthetized dogs.2. After three successive intravenous injections of propranolol, 0.5 mg/kg, had reduced the heart rate by 25%, a fourth dose had no further negative chronotropic action, but amiodarone, 10 mg/kg intravenously, at this point reduced the heart rate by 23%.3. Amiodarone, 10 mg/kg intravenously, reduced, but did not abolish, cardiac responses to isoprenaline, 2 mug/kg intravenously. Subsequent successive injections of 10 mg/kg of amiodarone did not further block the responses to isoprenaline, but propranolol, 1 mg/kg intravenously, abolished them.4. Amiodarone reduced cardiac chronotropic and inotropic responses to glucagon, which were not affected by propranolol.5. Cardiac output was increased 5 min after amiodarone, 10 mg/kg intravenously, but at 10 min and thereafter it did not differ from control values. Propranolol, 1 mg/kg intravenously, reduced cardiac output by 17% at 5 min, and by 30% after 30 min.6. From this and other evidence which is discussed, it is concluded that the cardiac actions of amiodarone are not produced by competitive blockade of beta-adrenoceptors.
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PMID:Cardiac actions in the dog of a new antagonist of adrenergic excitation which does not produce competitive blockade of adrenoceptors. 548 43

1. The inotropic activity of glucagon was compared with catecholamines and cardiac glycosides by in vitro procedures which were able to differentiate between the activities of the latter two groups.2. The frequency-force curve for glucagon resembled that of noradrenaline at low stimulation frequencies (1 and 2/min) and that of ouabain at more rapid frequencies of stimulation.3. Noradrenaline and adrenaline increased the amplitude of contraction of cat papillary muscles and markedly shortened the time to reach peak tension. Ouabain and glucagon increased tension without any change in the time to peak tension.4. Noradrenaline caused a rapid onset and rate of rise of contraction of cat aortic strips, whereas the response to ouabain was slow in onset and rate of development. Glucagon had no effect on this preparation, even at high concentrations.5. Manganese ions caused a shift of the dose-response curve to ouabain and glucagon, but not to noradrenaline or calcium. In 0.5 mM Ca media, the response to ouabain was abolished and the curve to noradrenaline shifted.6. When glucagon was added to an atrial preparation, the time to the initial increase in tension and the time to maximal tension was intermediate between that necessary for noradrenaline and that necessary for cardiac glycosides.7. Propranolol blocked the inotropic response to noradrenaline, but not to either ouabain or glucagon.8. A relative measure of contraction-dependency was described. Cardiac glycosides exhibited a greater degree of contraction-dependency than either noradrenaline or glucagon.9. Adrenaline elevated the depressed plateau of the action potential from calf and sheep Purkinje fibres, but ouabain and glucagon were without effect.10. Electrophysiological measurements demonstrated that moderate concentrations of glucagon exerted only a small effect in prolonging atrial and ventricular action potentials.11. Several pharmacological blocking drugs and other inotropic agents did not potentiate or block the inotropic response to glucagon. Reserpine pretreatment increased the response to glucagon.12. It was concluded that glucagon has its own spectrum of inotropic activity and does not completely mimic the effects of either ouabain or noradrenaline.
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PMID:Comparison of the inotropic response to glucagon, ouabain and noradrenaline. 549 91

Two beta-blocking agents, non-selective propranolol and beta1-selective metoprolol, were investigated with respect to their effects on glucose metabolism in 10 hypertensive patients with non-insulin dependent diabetes mellitus (NIDDM). The patients were treated randomly for two weeks in double-blind cross-over manner with (a) propranolol, (b) metoprolol, and (c) placebo. Propranolol impaired glucose tolerance when compared to placebo. The increase in blood glucose was associated neither with changes in concentrations of serum insulin, plasma glucagon of free fatty acid nor with alterations in peripheral insulin sensitivity as measured by 125I-insulin binding to mononuclear leukocytes. Although metoprolol had no effect on blood glucose, it increased 125I-insulin binding to mononuclear leukocytes. The increase in insulin binding could contribute to blood glucose control during metoprolol treatment. In search for reasons for poor metabolic control in NIDDM, treatment with non-selective beta-blockers should be kept in mind.
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PMID:Influence of beta-blocking drugs on glucose metabolism in patients with non-insulin dependent diabetes mellitus. 612 39

This study was conducted to characterize the mechanisms of hyperglycaemia in exercising sheep. Sheep were run on a treadmill for 45 min (5.5 km h-1, 8% incline) during adrenergic blockade (propranolol or phentolamine mesylate infusions) and during suppression of the rise in glucagon by infusion of somatostatin (SRIF). Propranolol did not alter the glucagon, insulin or glucose responses, except it tended to increase the metabolic clearance of glucose, presumably as a result of blocking the beta-adrenergic inhibition of glucose uptake. Phentolamine mesylate administration was associated with a suppression of the rise in glucagon concentrations, a reversal of alpha-adrenergic inhibition of insulin release and a reduction in glucose appearance during exercise. SRIF prevented the rise in glucagon and reduced insulin concentrations to below resting values. Propranolol and phentolamine mesylate did not alter the glucagon, insulin or glucose response to SRIF. However, SRIF prevented the insulin rise that occurred during phentolamine administration. The increment in glucose appearance produced in response to exercise was the same for SRIF, plus phentolamine mesylate and phentolamine mesylate in the first 25 min of exercise, but was significantly less than in the controls. During the last 20 min of exercise, glucose appearance was not significantly different from the control for any of the groups. The depression by SRIF and alpha-adrenergic blockade of the increment in glucose appearance due to exercise was associated with an impairment of the glucagon response. It appears, therefore, that glucagon may stimulate glucose production early in exercise in sheep directly, as well as by having a permissive effect.
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PMID:Effects of somatostatin and adrenergic blockade on glucagon, insulin and glucose in exercising sheep. 612 38

The effects of adrenergic stimulation and suppression on somatostatin (SS), insulin, and glucagon release were studied in intact dogs. Isoproterenol, a beta-adrenergic agonist, significantly increased portal venous and arterial levels of SS and arterial levels of insulin and glucagon. Propranolol, a beta-adrenergic antagonist, significantly decreased portal venous SS and suppressed the isoproterenol-stimulated increases in the levels of SS, insulin, and glucagon. alpha-Adrenergic stimulation (propranolol plus epinephrine) decreased portal venous SS and arterial insulin. Phentolamine, and alpha-adrenergic antagonist, increased portal venous and arterial SS and arterial glucagon. These data suggest that in intact dogs, stimulation of beta-adrenergic receptors enhances the release of SS, insulin, and glucagon, while stimulation of alpha-adrenergic receptors inhibits the release of SS and insulin without having a definitive effect on glucagon.
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PMID:Adrenergic control of somatostatin release. 612 51

The effects of alpha-, beta- or alpha + beta-adrenergic blockade on arterial plasma concentrations of insulin, glucagon and somatostatin in response to splanchnic nerve stimulation were studied in anesthetized cats. In control experiments splanchnic nerve stimulation caused a marked rise in plasma glucose and glucagon concentrations and a marked fall in insulin but somatostatin was unaffected. Pretreatment with phentolamine significantly increased basal plasma insulin concentration but the response pattern to splanchnic nerve stimulation was not altered. Propranolol attenuated both the glucose and insulin responses. Combined alpha-and beta-blockade abolished the hyperglycemia and hypoinsulinemia induced by splanchnic nerve stimulation, whereas the rise in plasma glucagon was not affected. It is concluded that insulin release from the pancreas and glucose release from the liver is controlled by adrenergic mechanisms whereas pancreatic glucagon and somatostatin secretion is relatively insensitive to splanchnic nerve stimulation in cats.
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PMID:Effects of adrenergic blockade on the release of insulin, glucagon and somatostatin from the pancreas in response to splanchnic nerve stimulation in cats. 613 9

Six normal humans each underwent infusions of 1) saline; 2) propranolol; 3) somatostatin; 4) somatostatin with propranolol; and 5) somatostatin with propranolol plus phentolamine on separate occasions. Propranolol alone had no effect on glucose production or plasma glucose. Somatostatin alone produced the expected initial decrease followed by an increase in both hepatic glucose production and plasma glucose. beta-Adrenergic blockade with propranolol displaced the glucose production (MANOVA, P = 0.0220) and plasma glucose (MANOVA, P = 0.0057) somatostatin response curves to higher levels, whereas alpha-adrenergic blockade with phentolamine combined with beta-adrenergic blockade displaced the glucose production (MANOVA, P = 0.0281) and plasma glucose (MANOVA, P = 0.0134) somatostatin response curves to lower levels. Because plasma insulin, C-peptide, and glucagon were suppressed comparably under all three conditions and plasma glucose concentrations were comparable initially, this represents direct alpha-adrenergic stimulation of hepatic glucose production in postabsorptive humans demonstrable when the primary glucoregulatory hormones are withdrawn and beta-adrenergic mechanisms are blocked. It is best attributed to sympathetic neural norepinephrine release.
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PMID:Direct alpha-adrenergic stimulation of hepatic glucose production in human subjects. 614 Aug 54

The effects of two beta-blocking drugs on endogenous insulin secretion and insulin sensitivity were investigated in a double-blind cross-over study in 13 hypertensive patients. The patients were randomly allocated to each of three 2-week treatment periods with propranolol 80 mg b.i.d., atenolol 50 mg b.i.d. and placebo b.i.d. Endogenous insulin secretion was assessed by measuring serum insulin and C-peptide before and 6 min after iv administration of glucagon; insulin sensitivity was determined by measuring insulin binding to erythrocytes, and as the glucose disappearance rate (KITT) after i.v. insulin. Fasting concentrations of serum free fatty acids (S-FFA) and plasma gastric inhibitory polypeptide (P-GIP) were also recorded during the three study periods. Both propranolol and atenolol reduced blood pressure, heart rate and S-FFA concentrations compared to placebo, and all patients showed measurable plasma concentrations of propranolol and atenolol. The results can be considered representative, therefore, of clinical beta-blockade. The two drugs did not significantly influence the fasting blood glucose level. There was an increase in fasting and glucagon-stimulated serum C-peptide concentration during propranolol therapy compared with placebo (p = 0.037 and p = 0.030, respectively), although this was not reflected by a significant change in serum insulin. Propranolol and atenolol did not significantly influence insulin binding to erythrocytes, but they clearly reduced the glucose disappearance rate KITT was compared to placebo (p = 0.0036 and p = 0.0003), respectively). The findings support the view that beta-blocking drugs can influence glucose metabolism by mechanisms other than inhibition of endogenous insulin secretion.
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PMID:Effect of beta-blocking drugs on beta-cell function and insulin sensitivity in hypertensive non-diabetic patients. 614 67

The effect of adrenergic agonists and antagonists on the secretion of gastric somatostatin-like immunoreactivity (SLI) and gastrin was investigated in an isolated, vascularly perfused rat stomach preparation. Two- to six-fold increases in SLI secretion induced by isoproterenol, epinephrine, and norepinephrine were completely abolished by propranolol but were not influenced by phentolamine. Propranolol did not alter glucagon- and DB-cAMP-induced stimulation of SLI release. Experiments in which the beta 2-agonist salbutamol and the beta 1- and beta 2-blockers practolol and H35/25 were used showed that both subtypes of beta receptors are involved. Gastrin secretion revealed only minor changes in dose-response studies with a wide range of isoproterenol concentrations (2 X 10(-8) to 1.5 X 10(-4) M). The results obtained in this study suggest that in rats 1) the SLI response to adrenergic agonism is predominantly mediated by beta receptors; 2) both beta 1- and beta 2-adrenergic receptors are involved; 3) under in vitro conditions, adrenergic agonism is a weak stimulus for gastrin secretion.
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PMID:Adrenergic control of rat gastric somatostatin and gastrin release. 614 72


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