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)

Studies on the mechanism of the hypoglycemia caused by the i.t. administration of morphine (40 micrograms) to nonfasted, unanesthetized mice included assessment of effects of i.t. morphine on circulating levels of immunoreactive insulin and glucagon, on body temperature, as well as testing the effects of i.p. pretreatment with antagonists of cholinergic, beta adrenergic, alpha-1 adrenergic, alpha-2 adrenergic, serotonergic and opioid receptors. Serum levels of insulin were not significantly affected at 30 and 60 min after i.t. morphine, but plasma glucagon levels were significantly increased at both time points. Rectal temperature decreased significantly in mice given either saline or morphine i.t., but there was no significant difference between the two groups over time. Atropine (2 mg/kg), propranolol (10 mg/kg), prazosin (2 mg/kg) and methysergide (2 mg/kg) did not affect morphine-induced hypoglycemia. Naloxone (20 mg/kg) antagonized i.t. morphine. Mecamylamine (2 mg/kg) produced a moderate hypoglycemia in control mice, which appeared to be additive to that caused by i.t. morphine. Yohimbine (1-4 mg/kg i.p.) also produced a moderate hypoglycemia in control mice, but caused a dose-related antagonism of i.t. morphine. The centrally active alpha-2 antagonist, L-657,743 (2S-trans)-1,3,4,5',6,6',7,12b-octahydro-1',3'-dimethylspiro -(2H-benzofuro- (2,3-a)quinolizine-2,4'(1'H)pyrimidin)-2-(3'H)-one hydrochloride) (4-20 mg/kg i.p.), but not the peripherally selective alpha-2 antagonist, L-659,066 (2R-trans)-N-(2-(1,3,4,6,7,12b-he xahydro-2'- oxospiro(2H-benzofuro(2,3-a) quinolizine-2,4-imidazolidin)-3'-yl)ethyl)methanesulfonamide hydrochloride) (4-20 mg/kg i.p.), caused a dose-related antagonism of i.t. morphine. The i.t. coadministration of yohimbine (2 or 10 micrograms) or L-659,066 (10 micrograms) with morphine exhibited no antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An insulin-independent mechanism of intrathecal morphine-induced hypoglycemia in mice: mediation through a central alpha-2 adrenergic pathway. 167 29

Yohimbine hydrochloride, an alpha 2-adrenoceptor antagonist, was administered (3.3 mg/kg i.v.) to anesthetized normal dogs provided with a T-shaped catheter inserted in the pancreaticoduodenal vein. The effects on blood glucose levels and pancreatic hormones were investigated. We show that yohimbine induced an immediate and pronounced stimulatory effect on insulin secretion accompanied by a clear decrease in blood glucose levels. Yohimbine also stimulated the pancreatic secretion of somatostatin and glucagon. However, the secretion kinetics were not the same for the three hormones: the stimulation was rapid and immediate for insulin and somatostatin, whereas it was progressive for glucagon. All these stimulatory effects were suppressed by propranolol, thus implicating beta-adrenergic mechanisms. Bilateral cervical vagotomy markedly reduced the immediate effect of yohimbine on insulin secretion, suggesting that a central neural pathway was implicated. In contrast, the progressive elevation in glucagon secretion was not decreased by vagotomy. Our results suggest that yohimbine stimulates, at least in part, insulin secretion by blocking central alpha 2-adrenoceptors.
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PMID:Involvement of a central nervous pathway in yohimbine-induced insulin secretion. 256 96

Effects of various alpha adrenergic agents on insulin release and cyclic 3':5'-adenosine monophosphate (cAMP) accumulation in pancreatic islets were investigated. Clonidine, epinephrine, alpha-methylnorepinephrine and norepinephrine were most potent and methoxamine and phenylephrine least potent in inhibiting the glucose-stimulated insulin release. Yohimbine and phentolamine were the most effective and prazosin was the least effective in antagonizing the epinephrine-inhibited insulin release. Clonidine markedly inhibited the glucagon-stimulated cAMP accumulation, whereas methoxamine showed weak inhibition. Yohimbine markedly increased cAMP accumulation in the presence of epinephrine, whereas prazosin showed little effect. The effects of alpha adrenergic agents on rabbit aorta contraction were also examined for comparison with alpha adrenergic receptors in pancreatic islets. In the aorta, the order of agonist potency was norepinephrine greater than phenylephrine greater than epinephrine greater than methoxamine greater than alpha-methylnorepinephrine and that of antagonist potency was prazosin greater than WB-4101 greater than phentolamine greater than dihydroergotamine greater than phenoxybenzamine greater than yohimbine. These orders of potencies were markedly different from those in pancreatic islets. These results clearly demonstrate that the alpha adrenergic receptors in rat pancreatic islets are different from those on rabbit aorta (alpha-1) and are typical postsynaptic alpha-2 adrenergic receptors.
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PMID:Postsynaptic alpha-2 adrenergic receptors in isolated rat islets of Langerhans: inhibition of insulin release and cyclic 3':5'-adenosine monophosphate accumulation. 611 Jul 70

The effects of adrenergic blockers on the glucagon response to insulin hypoglycemia were investigated in diabetic (10-15 days poststreptozocin [STZ] injection) and age-matched control rats. alpha-(Phentolamine nonspecific but predominantly alpha 1), alpha 2-(yohimbine), or beta-(propranolol) adrenergic blockers alone or in combination did not affect plasma glucose levels or plasma glucagon concentrations, in the basal state, in either control or diabetic rats. None of these adrenergic blockers, alone or in combination, inhibited the glucagon response to insulin hypoglycemia in control or diabetic rats. On the contrary, in control rats, the beta-adrenergic blocker alone or in combination with an alpha-adrenergic blocker and in diabetic rats, the alpha-adrenergic blocker alone significantly stimulated the glucagon response to insulin hypoglycemia. Second, the effects of yohimbine on the glucagon response to epinephrine infusion were studied in both young and old rats. Recently, Cherksey et al. (Proc. Soc. Exp. Biol. Med. 1982; 171:196-200) have reported that the adrenergic receptors on rat pancreatic islet cells are of the alpha 2-subtype. Yohimbine (alpha 2-adrenergic blocker) completely blocked the glucagon response to epinephrine infusion in both young and old rats, but had no inhibitory effect on the glucagon response to insulin hypoglycemia in control and short-term diabetic rats. From these observations, it could be inferred that the lack of glucagon response to insulin hypoglycemia in long-term diabetic rats is unlikely to be explained by an impairment of an adrenergic function.
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PMID:Role of sympathetic nervous system in glucagon response to insulin hypoglycemia in normal and diabetic rats. 638 31

This study aimed to compare the antagonistic effects of atipamezole (40,120, and 320 microg/kg, IM), yohimbine (110 microg/kg, IM), and saline on neurohormonal and metabolic responses induced by medetomidine (20 microg/kg, IM). Five beagle dogs were used in each of the 5 experimental groups in randomized order. Blood samples were taken for 6 h. Medetomidine significantly decreased norepinephrine, epinephrine, insulin, and nonesterified fatty acid levels, and increased plasma glucose levels. Both atipamezole and yohimbine antagonized these effects. The reversal effect of atipamezole was dose-dependency, except on epinephrine. Yohimbine caused prolonged increases in plasma norepinephrine and insulin levels compared to atipamezole, possibly because of its longer half-life elimination. Only yohimbine increased the cortisol levels. Neither glucagon nor lactate levels changed significantly. Based on these findings, when medetomidine-induced sedation is antagonized in dogs, we recommend using atipamezole IM, from 2- to 6-fold the dose of medetomidine, unless otherwise indicated.
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PMID:The antagonistic effects of atipamezole and yohimbine on stress-related neurohormonal and metabolic responses induced by medetomidine in dogs. 1252 32

In humans, glucagon-like peptide-1 (GLP-1) delays gastric emptying by inhibiting vagal activity and also increases gastric volumes, by unclear mechanisms. Because GLP-1 inhibits intestinal motility by stimulating the sympathetic nervous system in rats, we assessed the effects of a GLP-1 agonist and yohimbine, an alpha(2)-adrenergic antagonist, on gastric volumes in humans. In this double-blind study, 32 healthy volunteers were randomized to placebo, a GLP-1 agonist, yohimbine or GLP-1 and yohimbine. Gastric volumes (fasting predrug and postdrug, and postprandial postdrug) were measured by (99m)Tc single photon emission computed tomography imaging. Plasma catecholamines and haemodynamic parameters were assessed. Compared with placebo, GLP-1 increased (P = 0.03) but yohimbine did not affect fasting gastric volume. However, GLP-1 plus yohimbine increased (P < 0.001) postprandial gastric accommodation vs placebo and vs GLP-1 alone [postprandial volume change = 542 +/- 29 mL (mean +/- SEM, placebo), 605 +/- 31 mL (GLP-1), 652 +/- 54 mL (yohimbine) and 810 +/- 37 mL (GLP-1 and yohimbine)]. Plasma noradrenaline and dihydroxyphenylglycol concentrations were higher for yohimbine vs placebo and for GLP-1 and yohimbine vs GLP-1. Yohimbine stimulates central sympathetic activity and in combination with GLP-1, augments postprandial accommodation in humans.
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PMID:Effects of glucagon-like peptide-1 and sympathetic stimulation on gastric accommodation in humans. 1772 92

Glucagon-like peptide-1 (GLP-1), an incretin, which is used to treat diabetes mellitus in humans, inhibited vagal activity and activated nitrergic pathways. In rats, GLP-1 also increased sympathetic activity, heart rate, and blood pressure (BP). However, the effects of GLP-1 on sympathetic activity in humans are unknown. Our aims were to assess the effects of a GLP-1 agonist with or without alpha(2)-adrenergic or -nitrergic blockade on autonomic nervous functions in humans. In this double-blind study, 48 healthy volunteers were randomized to GLP-1-(7-36) amide, the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine acetate (l-NMMA), the alpha(2)-adrenergic antagonist yohimbine, or placebo (i.e., saline), alone or in combination. Hemodynamic parameters, plasma catecholamines, and cardiac sympathetic and parasympathetic modulation were measured by spectral analysis of heart rate. Thereafter, the effects of GLP-1-(7-36) amide on muscle sympathetic nerve activity (MSNA) were assessed by microneurography in seven subjects. GLP-1 increased (P = 0.02) MSNA but did not affect cardiac sympathetic or parasympathetic indices, as assessed by spectral analysis. Yohimbine increased plasma catecholamines and the low-frequency (LF) component of heart rate power spectrum, suggesting increased cardiac sympathetic activity. l-NMMA increased the BP and reduced the heart rate but did not affect the balance between sympathetic and parasympathetic activity. GLP-1 increases skeletal muscle sympathetic nerve activity but does not appear to affect cardiac sympathetic or parasympathetic activity in humans.
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PMID:Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans. 1859 8