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)

Cholinergic agents are potent modulators of insulin release that act via muscarinic receptors. We now investigated the muscarinic receptor subtype present in rat pancreatic islets in binding and functional studies. Binding of 5 nM [3H]N-methylscopolamine ([3H]NMS) was half maximal at 30 min. At 60 min, the maximal total binding was 1.29% and the non-specific binding (presence of 100 microM atropine) was 0.18% of the total radioactivity per 10 micrograms islet protein. Unlabelled atropine inhibited [3H]NMS binding with an IC50 of ca. 30 nM. The rank order of antagonist high-affinity binding was atropine greater than sila-hexocyclium methyl sulfate (SiHC; M1 greater than M3 greater than M2) greater than pirenzepine (M1 greater than M2 approximately M3) = methoctramine (M2 greater than M1 greater than M3). The high-affinity Kds were 8.5, 56, 1300 and 1300 nM, respectively. The high affinity Kd of the muscarinic receptor agonist, arecaidine propargyl ester (APE), was 8.1 nM. The EC50 for the biological effects of APE on insulin and glucagon secretion was 3.2 and 2.3 nM. The rank order for the high-affinity biological effects of antagonists (inhibition of APE-mediated insulin/glucagon release) was almost the same as for binding. The data indicate that rat pancreatic islets contain neither an M1 subtype (high-affinity for pirenzepine) nor an M2 subtype (high-affinity for methoctramine) receptor. However, the data evidence an M3 receptor subtype, since SiHC in the absence of the M1 receptor subtype shows a relatively high affinity to the receptors in rat pancreatic islets.
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PMID:Muscarinic receptor subtypes in rat pancreatic islets: binding and functional studies. 218 4

We hypothesized the existence of vagal arginine sensors in the liver which modulate arginine-induced pancreatic hormone secretion. The present study was carried out to examine the efferent pathways and receptor mechanisms from arginine sensors using selective vagotomies and autonomic drugs on the secretion of insulin and glucagon after ip injection of L-arginine (1 g/kg BW) in rats in an unanesthetized and unrestrained state. Hepatic vagotomy (sectioning of the hepatic branch of the vagus nerve) enhanced both plasma insulin and glucagon concentrations after ip arginine more than those in sham-vagotomized (control) rats. The effect of hepatic vagotomy was blocked by adding celiac vagotomy (sectioning of the celiac branches of the vagus nerve) or by previous administration of atropine methyl nitrate (10 mg/kg BW), but not by phentolamine (1 mg/kg BW) or propranolol (2 mg/kg BW). Celiac vagotomy alone did not affect the plasma insulin concentration; however, it reduced the plasma glucagon concentration after ip arginine compared to that in sham-vagotomized rats. Administration of atropine alone did not affect plasma insulin or glucagon concentrations after ip arginine. These results suggest that celiac branches of the vagus nerve act as efferent pathways to the pancreas through a muscarinic receptor mechanism in the hepatic arginine sensor-mediated pancreatic neuroendocrine system. The physiological role of these hepatic sensors may be to prevent arginine-induced exaggerated pancreatic hormone secretion and maintain blood glucose homeostasis.
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PMID:Modulation of arginine-induced insulin and glucagon secretion by the hepatic vagus nerve in the rat: effects of celiac vagotomy and administration of atropine. 220 80

We previously reported that neostigmine injected into the third cerebral ventricle stimulated adrenal secretion of epinephrine, secretion of glucagon from the pancreas, and direct neural innervation of the liver, resulting in hepatic venous plasma hyperglycemia in anesthetized fed rats. However, receptor type of these 3 mechanisms is not known. Therefore, we examined the effects of intraventricularly injected cholinergic or adrenergic antagonists on neostigmine-induced catecholamines in intact rats, glucagon secretion which is mediated by direct neural innervation of pancreas in bilateral adrenalectomized (ADX) rats, and hepatic venous hyperglycemia which is mediated by direct neural innervation of liver in ADX rats receiving constant infusion of somatostatin from femoral vein. Atropine injected into the third cerebral ventricle suppressed epinephrine secretion and dose-dependently inhibited hepatic venous hyperglycemia induced by neostigmine in intact rats. The neostigmine-induced glucagon secretion which occurs in ADX rats was suppressed by atropine. Atropine also prevented the neostigmine-induced hyperglycemia in ADX rats receiving constant somatostatin infusion through femoral vein (ADX-Somato rats). On the other hand, phentolamine, propranolol and hexamethonium showed no significant inhibitory effect on neostigmine-induced hyperglycemia, epinephrine and glucagon secretion in intact rats, glucagon secretion in ADX rats, or hyperglycemia in ADX-Somato rats. These results suggest that neostigmine-induced epinephrine and glucagon secretion and increased hepatic glucose output stimulated by direct neural innervation to liver is mediated by central muscarinic receptor in fed rats.
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PMID:Neostigmine-induced hyperglycemia is mediated by central muscarinic receptor in fed rats. 233 69

Pancreatic hormone release is generally thought to be regulated through adrenergic as well as muscarinic receptors. We have previously observed possible nicotinic involvement in insulin release. In the present study, we incubated isolated rat islets for 60 min with various concentrations of atropine (a muscarinic receptor blocker), alpha-bungarotoxin (alpha-Btx, a nicotinic receptor blocker), and anti-acetylcholine receptor antibody (IgG) (anti-Ach.R.Ab) obtained from a patient with myasthenia gravis. Atropine suppressed insulin release, and alpha-Btx and anti-Ach.R.Ab potentiated it; atropine did not suppress glucagon release, while alpha-Btx and anti-Ach.R.Ab raised it. None of these agents influenced somatostatin release. These observations suggest that muscarinic as well as nicotinic receptors influence insulin release, as nicotinic receptors do glucagon release. Neither nicotinic nor muscarinic receptors seem to regulate somatostatin release.
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PMID:Participation of nicotinic receptor in hormone release from isolated rat islets of Langerhans. 256 21

Ambient glucose stimulates insulin but inhibits glucagon secretion. We investigated whether mirror-image regulation pertains also to glucose effects on muscarinic receptor binding to B and A cells. We compared binding of [3H]methylscopolamine to islets from normal guinea pigs and to A-cell rich islets from streptozotocin-treated animals. Binding was assessed in intact islets at 37 C after previous culture for 72 h in 3.3, 5.5, or 11 mM glucose. For both types of islets, specific binding was observed after 1 min and reached a plateau after 10 min of incubation. Half-maximal displacement of 2.8 X 10(-9) M [3H] methylscopolamine occurred with 10(-9) - 10(-8) M unlabeled methylscopolamine. In normal islets, specific binding was significantly higher after culture in 11 mM than after 3.3 or 5.5 mM glucose. Conversely, in A-cell rich islets, binding was significantly higher at 3.3 or 5.5 than at 11 mM glucose. Glucagon release induced by acetylcholine (10(-5) M) was half-maximally suppressed by methylscopolamine at a concentration of 10(-9) - 10(-8) M. Acetylcholine-stimulated glucagon release was higher from A-cell rich islets when cultured at 3.3 mM than when cultured at 11 mM glucose. It is concluded: 1) that both A and B cells appear to contain muscarinic receptors, 2) that long term glucose environment exerts opposite effects on binding of methylscopolamine to A and B cells, and 3) that inhibition of binding to A cells is correlated with reduction of acetylcholine-induced glucagon release.
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PMID:Glucose exerts opposite effects on muscarinic receptor binding to A and B cells of the endocrine pancreas. 388 67

Previously, we reported that pancreatic acini have specific receptors for the insulin-like growth factors (IGF) I and II. We now report that the binding of 125I-labeled IGF II to mouse pancreatic acini is maximally increased by 100 nM insulin (51%) and is maximally reduced by 10 nM cholecystokinin octapeptide (CCK8) (34%), but is not affected by other regulatory peptides such as somatostatin or glucagon. Since many polypeptide hormones are internalized, we determined whether this regulation of IGF II binding occurred via a change in internalization. Acid washing or trypsinization has been shown to remove surface-bound hormone while the acid- or trypsin-resistant radioactivity represents internalized radioligand. Insulin increased and CCK8 decreased the internalization of IGF II as determined by these techniques. Studies of IGF II binding to acini at low temperature (15 degrees C) and binding to particulate fractions from acini were also consistent with the effect of insulin to increase and CCK8 to decrease the internalization of IGF II. When insulin and CCK8 were added together, the inhibitory effect of CCK8 predominated, indicating that CCK8 acted distal to the effect of insulin. Several lines of evidence suggest that this effect of CCK8 was via the CCK receptor and was mediated via a change in intracellular Ca2+: the effect of CCK8 on inhibiting IGF II binding was blocked by the cholecystokinin antagonist N2,O2'-dibutyryl cGMP; the cholinergic agent carbachol (1-100 microM), which acts through the muscarinic receptor to increase intracellular Ca2+, also inhibited IGF II binding; the Ca2+ ionophore A23187 (1-5 microM) mimicked the effects of CCK8 and carbachol. These data indicate, therefore, that CCK8 and possibly insulin may regulate the internalization of IGF II via intracellular Ca2+. Moreover, the data raise the possibility that alterations of hormone internalization may be a general phenomenon of hormone-hormone interaction.
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PMID:Effect of intracellular Ca2+ on insulin-like growth factor II. internalization into pancreatic acini. Roles of insulin and cholecystokinin. 609 32

The effect of cholinergic stimulation on gastric acid secretion was examined in mongrel dogs using an in vivo and an in vitro preparation for comparison. The gastric fistula dog was used for the in vivo studies, and methacholine was infused directly into the artery supplying the fundus of the stomach to avoid systemic hemodynamic changes. Isolated parietal cells were used for the in vitro studies. In vivo, methacholine infused at 1 microgram/min was found to stimulate gastric acid secretion that was inhibited 98.5 +/- 1.4% by intravenously administered metiamide (H2 blocker) and 72 +/- 11% by intra-arterially administered glucagon. Glucagon had no effect on histamine stimulated acid secretion. In vitro, increasing concentrations of methacholine from 10(-7), 10(-6) to 10(-5) M stimulated [14C]aminopyrine uptake into parietal cells in a concentration dependent manner. This effect of methacholine was unaltered by 10(-4) M metiamide or 10(-6) M glucagon. However, atropine 10(-5) M totally blocked the stimulatory effect of methacholine. Our data suggest that the cholinergic mechanism of acid secretion is different when examined in vivo vs. in vitro even in the same species. In vivo histamine dependency has a major contribution to the cholinergic mechanism of acid secretion, whereas in vitro the interaction of the cholinergic agonist at the muscarinic receptor results in acid stimulation that does not require the presence of histamine.
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PMID:Cholinergic mechanism of acid secretion in the dog: an in vivo and in vitro comparison. 652 81

Propionate (0, 1, 2, 4, 8, 16, 32, and 64 mumol.kg BW-1 x min-1 for 30 min) was infused i.v. to investigate the physiological effects of propionate on insulin and glucagon responses in sheep. An i.v. propionate infusion (32 mumol.kg BW-1 x min-1 for 30 min) with adrenergic and cholinergic blockades was also conducted to clarify the role of autonomic innervation in the control of propionate-induced insulin and glucagon responses. In the experiment in which we studied responses to propionate infusion, the concentrations of plasma insulin and glucagon during propionate infusion increased (P < .05) from the preinfusion concentrations at infusion rates of > 4 and 8 mumol.kg BW-1 x min-1, respectively. The incremental response areas of plasma insulin and glucagon during propionate infusion increased (P < .05) at infusion rates of > 16 and 32 mumol.kg BW-1 x min-1, respectively. In the experiment studying the effects of adrenergic and cholinergic blockades on responses to propionate, the insulin incremental response area during propionate infusion was suppressed (P < .05) by atropine infusion but it was not influenced by phentolamine, propranolol, or hexamethonium infusions. The glucagon response area was suppressed (P < .05) by phentolamine infusion, but it was not influenced by propranolol, atropine, or hexamethonium infusions. It is concluded that in sheep 1) propionate may have a physiological role in stimulating insulin and glucagon responses, 2) the propionate-induced insulin response is partly due to the parasympathetic nervous system through activation of a muscarinic receptor, and 3) the propionate-induced glucagon response is stimulated by adrenergic alpha-receptors.
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PMID:Plasma insulin and glucagon responses to intravenous infusion of propionate and their autonomic control in sheep. 790 90

Effects of muscarinic receptor blockade (atropine), stimulation (bethanechol), and bowel smooth muscle relaxant (glucagon) on the urodynamics of the continent cecal urinary reservoir in a tube form and after complete, partial, and sham detubularizations were studied using dogs. Complete detubularization significantly increased capacity and decreased spontaneous motor activity, whereas the other types of detubularization had no significant effects on them. Neither atropine nor glucagon had influence on the basal pressure, but they increased the capacity and the volume at which the first pressure wave appeared and decreased the wave amplitude. After detubularization glucagon further decreased uninhibited contractions while atropine totally abolished them. The highest capacity and lowest motor activity was gained when atropine or glucagon was given in cases with detubularized pouch demonstrating an additive effect of the detubularization and drug. Also, bethanechol increased the motor activity and decreased the volume in detubularized problem in a patient with a detubularized cecal pouch, orally administered anticholinergic or bowel smooth muscle relaxing drugs may be useful in management.
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PMID:Effects of atropine, glucagon, and bethanechol on urodynamics of continent cecal urinary reservoir before and after complete, partial, and sham detubularizations in dog. 809 55

Expression of muscarinic receptor subtypes in rat gastric smooth muscle was examined with reverse transcriptase-polymerase chain reaction (RT-PCR). Under the condition for detecting the messages of m1-m4 subtypes in brain, atrium, and gastric mucosa, only the fragments of m2 and m3 subtypes were amplified with RNA prepared from rat gastric smooth muscles. Furthermore, the amplified fragments were digested by restriction enzymes, reconfirming that the predicted size products of m2 and m3 contain the partial DNA sequences of m2 and m3 subtypes, respectively. We measured gastric motility in rats with a pressure transducer system under the continuous venous infusion of the muscarinic antagonists atropine and butylscopolamine (nonselective), AF-DX 116 (M2), zamifenacine (M3), and glucagon. Heart rate was monitored simultaneously in the tail. Gastric motility was inhibited in the presence of glucagon and zamifenacine without alteration of heart rate, whereas there was no inhibition in the presence of AF-DX 116 even after the augmentation of heart rate was observed. Gastric emptying was also suppressed in the presence of zamifenacine, which had an effect comparable with that of atropine, butylscopolamine, and glucagon. These results indicate that the activation of the M3 subtype in gastric smooth muscle causes its contraction, and the M3 selective antagonist could be a potentially useful drug without an adverse effect on the heart for radiological and endoscopic examination in the upper gastrointestinal tract.
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PMID:Expression of muscarinic receptor subtypes in rat gastric smooth muscle: effect of M3 selective antagonist on gastric motility and emptying. 914 41


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