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 role of opiate receptors in the metabolic response to an intravenous glucose load was determined in eight non-diabetic subjects (four of whom showed a positive chlorpropamide alcohol flush response and four who did not). Subjects were studied in a double blind randomised fashion receiving either a saline control or the specific opiate receptor antagonist, naloxone (0.4 mg/min), as an infusion for 5 minutes before and 20 minutes after an intravenous bolus of glucose (0.5 g/kg body weight). Naloxone decreased the early plasma glucose peak in all subjects by increasing the distribution volume but did not alter the fractional glucose clearance. Insulin and glucagon responses to glucose were not altered by naloxone. Naloxone delayed the normal post-glucose rise in the levels of the gluconeogenic precursors alanine, lactate, pyruvate and glycerol suggesting a delay in the usual inhibition in gluconeogenesis following a glucose load. There was no difference in the metabolic response between those subjects who were liable to chlorpropamide alcohol flushing and those who were not either with or without naloxone. We conclude that opiate receptors may influence distribution volume and gluconeogenesis but do not play a major role in either insulin or glucagon secretion or in glucose disposal following an intravenous glucose load.
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PMID:Opiate receptors and the metabolic response to intravenous glucose. 629 13

Catheterization of the portal vein and stereotaxic implantation of electrodes in the lateral hypothalamic area (LHA) were performed in normal rats after thiopental anesthesia. Immunoreactive glucagon (IRG) and insulin (IRI), glucose, catecholamines, and beta-endorphin were monitored in portal and peripheral plasma, before and during electrical stimulation of the LHA. The influences on glucose and hormone concentrations of propranolol, phentolamine, atropine, and naloxone infusions were also investigated in similar rats. A basal portoperipheral concentration gradient was found for IRG, IRI, and catecholamines, but not for beta-endorphin. The LHA stimulation induced a significant rise in portal catecholamine, IRG, and glucose concentrations; IRI remained unchanged; the portoperipheral catecholamine gradient was augmented. These alterations were not observed after bilateral splanchnicectomy. Propranolol infusion abolished the LHA-dependent IRG and glucose rises. Naloxone reduced the IRG rise significantly. Phentolamine and atropine did not modify the LHA-induced reactions. These results suggest that the glucagon release which follows LHA electrical stimulation depends mainly on beta-adrenergic transmission by the splanchnic nerves. Opioid peptide receptors may modulate this effect.
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PMID:Glucagon release after stimulation of the lateral hypothalamic area in rats: predominant beta-adrenergic transmission and involvement of endorphin pathways. 630 29

To evaluate a possible role for endogenous opiates in modulating sympathetic-adrenal function in humans, we measured plasma epinephrine and norepinephrine (radioenzymatic method), blood pressure and heart rate in 8 normal men (aged 24-33 years) before and after placebo or different doses (0.4, 4.8, 10 mg) of naloxone. In 6 subjects plasma insulin and glucagon levels were also measured by radioimmunoassay after placebo and 10 mg naloxone. Naloxone had no significant effect upon blood pressure, heart rate, plasma insulin, glucagon or norepinephrine. Placebo, 0.4 and 4.8 mg naloxone caused no significant change in peripheral levels of epinephrine while 10 mg produced an increase in epinephrine concentrations 15 min after iv injection (186 +/- 23 vs 99 +/- 9 pmol/l, P less than 0.01). Since naloxone did not modify plasma levels of insulin and glucagon, an indirect effect of naloxone on adrenal medullary secretion seems to be excluded. These results are in agreement with in vitro experimental data obtained in animals and suggest that endogenous opiates also have a role in modulating adrenal medullary secretion in man.
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PMID:Effects of naloxone on catecholamine plasma levels in adult men. A dose-response study. 633 Oct 37

The role of endogenous opioid peptides in mediating the endocrine and metabolic response to pelvic surgery was investigated. Fourteen patients were studied; seven were infused with the specific opioid antagonist, naloxone, at a rate of 20 micrograms kg-1 (body weight) hr-1, while the remainder acted as a control group. Naloxone exacerbated the glycaemic response to surgery but had no statistically significant effect on changes in the glycoregulatory hormones, pancreatic glucagon, insulin, cortisol and growth hormone. However, there was a wide individual variation in the glucagon response to naloxone with marked stimulation in some patients. Naloxone infusion increased plasma pancreatic polypeptide secretion during the 1st hour of surgery and reversed the decline in plasma motilin concentrations, but had no effect on circulating somatostatin, vasoactive intestinal polypeptide, gastrin, enteroglucagon and neurotensin values. We conclude that endogenous opioid peptides have only a limited role in modulating the endocrine and metabolic response to surgery.
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PMID:The effects of naloxone on circulating metabolites, glycoregulatory hormones and gut peptides during pelvic surgery. 668 26

A specific arousal therapy with NAGD (Naloxone, Activated Charcoal, Glucagon, Doxapram) is outlined for victims of drug overdose in comatose and semi-comatose states. Several direct benefits accrue if early awakening or lightening of such patients is safely accomplished. There are: 1) elimination of need for prolonged intubation or tracheostomy; 2) patient's ability to tell which drug(s) were taken; 3) excessively frantic and vigorous supportive treatment is obviated; and 4) the overall hospital stay is shortened. The NAGD regimen has been found to effectively, safely, and predictably reverse coma. Therapy consists of: naloxone 0.8 mg to 1.6 mg intravenously; large-bore orogastric tube instillation of 100 gm to 120 gm activated charcoal slurry; glucagon 1 mg to 2 mg intravenously; and, in selected cases, doxapram 1 mg/kg to 2 mg/kg intravenously.
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PMID:NAGD regimen for the coma of drug-related overdose. 739 49

The concentrations of beta-endorphin, ACTH, insulin (IRI), glucagon (IRG), cortisol and growth hormone were determined by radioimmunoassay during oral glucose tolerance test (OGTT) performed in 13 obese patients with normal glucose tolerance and without arterial hypertension. The test was performed in random, before and after intravenous administration of 0.8 mg of naloxone. Six persons with normal body weight served as controls. Higher basal concentrations of beta-endorphin and significant increase in beta-endorphin levels during OGTT, without concomitant increase in ACTH concentrations, have been found in obese patients. No effect of naloxone on beta-endorphin liberation during OGTT was observed, though the drug caused lowering in maximal increment of beta-endorphin and paradoxically lowered the concentrations of ACTH and cortisol. The basal concentrations of beta-endorphin did not correlate with the concentrations of insulin, ACTH, cortisol and growth hormone. Elevated concentrations of insulin, lowered concentration of growth hormone and normal levels of glucose and glucagon were observed in basal conditions, and excessive responses of insulin, glucose and glucagon were observed in obese patients during OGTT. Naloxone lowered insulin response and inhibited the fall of growth hormone during OGTT but did not influence the concentrations of glucose and glucagon. No correlation was found during OGTT after naloxone between insulin and beta-endorphin, ACTH or cortisol, whereas negative correlation was observed between insulin and growth hormone. The obtained results suggest that the elevated concentrations of beta-endorphin in simple obesity may be of both hypophyseal and peripheral origin. Hyper-beta-endorphinemia observed in obesity is probably not directly responsible for hyperinsulinemia, it may, however, be responsible for lower sensitivity of tissues to the action of insulin.
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PMID:[Effect of naloxone on beta-endorphin and insulin concentrations during glucose tolerance testing in patients with simple obesity]. 805 20

Liraglutide, an acylated analog of glucagon-like peptide 1 (GLP-1), could improve glycemic control in diabetes. Moreover, endogenous opioid peptides play a role in blood sugar regulation. Since GLP-1 receptors are also expressed in extra-pancreatic tissues, this study investigates the effect of liraglutide on endogenous opioid secretion in type 1-like diabetes. The endogenous opioid level was determined by enzyme-linked immunosorbent assay. The direct effect of liraglutide on endogenous opioid secretion was determined in the isolated adrenal medulla. Acute treatment with liraglutide dose-dependently attenuated hyperglycemia, and increased the plasma opioid neuropeptide, beta-endorphin (BER) levels in diabetic rats. These effects have been blocked by GLP-1 receptor antagonist, naloxone. Additionally, the effects of liraglutide were markedly reduced in adrenalectomized diabetic rats. In the isolated adrenal medulla, liraglutide induced BER secretion and increased the BER mRNA levels. Subcellular effects of liraglutide on the adrenal gland were further identified to mediate through the exchange proteins directly activated by cAMP, mainly using the pharmacological blockade. After repeatedly administering liraglutide, metabolic changes in diabetic rats were investigated, and genes associated with gluconeogenesis in the liver were downregulated. Naloxone pretreatment inhibited these effects of liraglutide, indicating the involvement of endogenous opioids. The present study indicated that liraglutide had an acute effect of reducing hyperglycemia by regulating endogenous opioid BER and modifying the glucose homeostasis.
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PMID:Liraglutide Activates Glucagon-Like Peptide 1 Receptor to Attenuate Hyperglycemia through Endogenous Beta-Endorphin in Diabetic Rats. 3323 92


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