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 effects of pirenzepine on the plasma concentrations of gut hormones in the fasting and postprandial states were studied in six healthy subjects. On separate days and in random order, 10 mg pirenzepine, in 2 ml of solvent, or 2 ml saline (0.15 mol/l) were given intravenously 30 min before a standard normal breakfast (2220 kJ). Pirenzepine was not found to affect basal or postprandial levels of insulin, glucagon, gastric inhibitory peptide (GIP), neurotensin, vasoactive intestinal peptide (VIP) or somatostatin. The basal concentration of pancreatic polypeptide (PP) was lowered (p less than 0.05) and the postprandial elevation reduced, though not significantly. While the basal concentration of motilin was also suppressed (p less than 0.05), the postprandial elevation remained unchanged following pirenzepine. The release of enteroglucagon was reduced significantly in the basal and postprandial states (p less than 0.05 and p less than 0.025 respectively). The postprandial gastrin response was prolonged slightly, but insignificantly, by pirenzepine. It is concluded that pirenzepine does not exert any major or unexpected actions on the hormonal control of digestion.
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PMID:The effect of pirenzepine on meal-stimulated gastrointestinal hormones. 611 82

To investigate the participation of cholinergic receptors in glucagon- and arginine-induced GH and PRL secretion, glucagon (1 mg, sc) and arginine (30 mg over 30 min) were administered to a group of normal subjects. On a different occasion, both tests were repeated after premedication with 40 mg pirenzepine, a muscarinic blocker, given iv 5 min before the test substances. Pirenzepine completely suppressed the glucagon- and arginine-induced GH rise in all subjects. The PRL response to arginine was not altered by pirenzepine. The results suggest that cholinergic muscarinic receptors regulate the GH response to glucagon and arginine in man.
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PMID:Participation of cholinergic muscarinic receptors in glucagon- and arginine-mediated growth hormone secretion in man. 689 69

Growth hormone (GH) hypersecretion has been described in diabetes mellitus and seems to be involved in the pathogenesis of diabetes complications. As pirenzepine (PZ), a cholinergic muscarinic antagonist, is able to inhibit GH hypersecretion in insulin-dependent diabetes mellitus (IDDM), we investigated whether PZ is also able to inhibit spontaneous and stimulated GH-release in non-insulin-dependent diabetes mellitus (NIDDM). Ten non-obese well-controlled patients with NIDDM underwent in random order the following three double-blind one week treatments: placebo (PL), PZ at low dose (PL in the morning plus PZ 50 mg at 22 h) or high dose (PZ 50 mg at 8 h plus 100 mg at 22 h). Pirenzepine administration significantly (p < 0.05) decreased nocturnal GH release after both low and high dose (AUC, PL vs PZ: 107.3 +/- 26.5 vs 48.3 +/- 10.5 and 57.6 +/- 9.6 micrograms/L/h, respectively). The GH response to arginine infusion was significantly inhibited by PZ at high dose (AUC, 147.1 +/- 48.8 vs 444.7 +/- 194.3 micrograms/L/h, p < 0.01), but not at low dose. Glucose, insulin, glucagon and somatostatin responses to arginine infusion were not changed by pirenzepine treatment. In conclusion, the muscarinic blockade by PZ is able to inhibit the spontaneous and stimulated GH secretion also in NIDDM without affecting insulin secretion.
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PMID:Pirenzepine decreases basal and stimulated GH secretion in patients with type 2 (non-insulin-dependent) diabetes mellitus. 800 63

Plasma levels of glucagon-like peptide-1 (GLP-1) rise rapidly after nutrient ingestion through an indirect mechanism triggered from the proximal intestine and involving the vagus nerve that stimulates the L cell in the distal gut. The role of muscarinic receptors in this pathway was thus investigated using the anesthetized rat and fetal rat intestinal cells (FRIC) in culture. GLP-1 secretion from the distal gut increased 5-fold after 3 ml corn oil were placed into the proximal duodenum (P < 0.001). Atropine (a nonspecific muscarinic receptor antagonist) completely inhibited fat-induced GLP-1 secretion in vivo (P < 0.01). Pirenzepine (an M1 muscarinic receptor antagonist) also inhibited fat-induced GLP-1 secretion in vivo, by 91 +/- 6% (P < 0.01). Gallamine (an M2 muscarinic receptor antagonist) and 4-diphenylacetoxy-N-methylpiperidine (an M3 muscarinic receptor antagonist) had no effect. Incubating FRIC cultures with bethanechol (a muscarinic receptor agonist) stimulated GLP-1 secretion to 200 +/- 22% of control (P < 0.01). Pirenzepine and gallamine significantly inhibited bethanechol-stimulated GLP-1 secretion, by 96 +/- 12% and 98 +/- 8%, respectively (P < 0.01). Unexpectedly, 4-diphenylacetoxy-N-methylpiperidine stimulated GLP-1 secretion by FRIC cells, to 324 +/- 52% of the control value (P < 0.01). Double immunofluorescent staining using GLP-1 and M1, M2, and M3 muscarinic receptor antibodies showed expression of the three subtypes of muscarinic receptors by the L cells in rat ileal sections and FRIC cultures. These results demonstrate the role of M1 muscarinic receptors expressed by L cells in the control of postprandial secretion of GLP-1. M2 muscarinic receptors also seem to play a role in controlling GLP-1 secretion by fetal, but not adult, L cells.
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PMID:Muscarinic receptors control postprandial release of glucagon-like peptide-1: in vivo and in vitro studies in rats. 1202 Dec 7

Glucagon-like peptide 1 (GLP-1) released from distal intestinal endocrine L cells after food intake is a potent glucose-dependent stimulant of insulin secretion. Plasma levels of GLP-1 rise rapidly after nutrient ingestion through an indirect mechanism triggered from the proximal intestine and involving the vagus nerve. Our previous studies showed the involvement of M1 muscarinic receptors expressed by the L cells in the regulation of postprandial GLP-1 secretion in rats. The goal of this study was to explore the involvement of muscarinic receptors in the regulation of GLP-1 secretion by human L cells using a newly described human L cell line (NCI-H716). Phorbol 12-myristate 13-acetate (positive control) stimulated GLP-1 secretion to 252 +/- 38% of the control (P < 0.001). Bethanechol, a nonselective muscarinic agonist, significantly stimulated GLP-1 secretion to 187 +/- 20% of the control (P < 0.01, n = 8). Pirenzepine (M1 antagonist; 10-1000 microM) and gallamine (M2 antagonist; 10-1000 microM) completely inhibited bethanechol-induced GLP-1 secretion, whereas 4-diphenylacetoxy-N-methylpiperidine (M3 antagonist) had no effect on bethanechol-stimulated GLP-1 secretion. McN-A-343 (M1 muscarinic agonist) dose dependently stimulated GLP-1 secretion (to 252 +/- 50% of control at 1000 microM; P < 0.01), whereas oxotremorine (M3 agonist) had no effect. M1, M2, and M3 muscarinic receptors were shown to be expressed in NCI-H716 cells by Western blot, immunohystochemistry, and RT-PCR. Expression of the M1, M2, and M3 muscarinic receptor subtypes was also confirmed in paraffin-embedded human small intestine sections by double immunofluorescent staining. These results demonstrate the role of M1 and M2 muscarinic receptors expressed by human L cells in the control of GLP-1 secretion.
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PMID:Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells. 1281 May 81

Muscarinic antagonists, particularly atropine, can inhibit myopia development in several animal models and also in children. However, the biochemical basis of the inhibition of axial eye growth remains obscure, and there are doubts whether muscarinic receptors are involved at all. Experiments in chickens and monkeys have shown that the synthesis of the transcription factor ZENK, also named Egr-1, in retinal glucagon amacrine cells is strongly associated with inhibition of axial eye growth (assumed to create a STOP signal). We have tested whether the muscarinic antagonists atropine, pirenzepine, oxyphenonium, gallamine, MT-3, himbacine, and 4-DAMP can stimulate ZENK expression so that the drugs' inhibitory effect on myopia development could be explained by an enhanced STOP signal. Because it is known that intravitreal quisqualic acid (QA) eliminates most cholinergic neurons in the retina within 6 or 7 days, in a second set of experiments, we tested whether these antagonists could still stimulate ZENK production, 6 days after QA was applied. Muscarinic antagonists, injected intravitreally at various concentrations, affected ZENK synthesis in various and unpredictable ways. Pirenzepine, oxyphenonium, and MT-3 increased the proportion of glucagon cells that were ZENK-immunoreactive, whereas himbacine decreased that proportion, and gallamine and 4-DAMP had no significant effect. Atropine caused an upregulation of ZENK only if all positive amacrine and bipolar cells were counted and therefore appeared to affect primarily cells other than glucagon amacrines. The pattern of results remained unchanged after ablation of most cholinergic neurons by QA. Our results suggest that at least some muscarinic antagonists do not activate cells that synthesize ZENK when they inhibit axial eye growth. Therefore, in line with other studies they also cast doubt on the assumption that muscarinic transmission is crucial, and they suggest that muscarinic antagonists may inhibit myopia through extraretinal target sites or through non-cholinergic retinal actions.
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PMID:Effects of muscarinic antagonists on ZENK expression in the chicken retina. 1614 26