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)

Oxytocin (OT) infusion in normal dogs increases plasma insulin and glucagon levels and increases rates of glucose production and uptake. The purpose of this study was to determine whether the effects of OT on glucose metabolism were direct or indirect. The studies were carried out in normal, unanesthetized dogs in which OT infusion was superimposed on infusion of either somatostatin, which suppresses insulin and glucagon secretion, or clonidine, which suppresses insulin secretion only. Infusion of 0.2 microgram/kg/min of somatostatin suppressed basal levels of plasma insulin and glucagon and inhibited the OT-induced rise of these hormones by about 60-80% of that seen with OT alone. The rates of glucose production and uptake by tissues, measured with [6-3H] glucose, were significantly lower than those seen with OT alone, and the rise in glucose clearance was completely inhibited. Clonidine (30 micrograms/kg, sc), given along with an insulin infusion to replace basal levels of insulin, completely prevented the OT-induced rise in plasma insulin and markedly reduced the glucose uptake seen with OT alone, but did not reduce the usual increase in plasma glucose and glucagon levels or glucose production. To determine whether the OT-induced rise in plasma insulin was in response to the concomitant increase in plasma glucose, similar plasma glucose levels were established in normal dogs by a continuous infusion of glucose and an OT infusion was superimposed. OT did not raise plasma glucose levels further, but plasma insulin levels were increased, indicating that OT can stimulate insulin secretion independently of the plasma glucose changes. Studies by others have shown that the addition of OT to pancreatic islets or intact pancreas can stimulate insulin and glucagon secretion, indicating a direct effect. Our studies agree with that and suggest that in vivo, OT raises plasma insulin levels, at least in part, through a direct action on the pancreas. These studies also show that OT increases glucose production by increasing glucagon secretion and, in addition, a direct effect of OT on glucose production is likely. The OT-induced increase in glucose uptake is mediated largely by increased insulin secretion.
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PMID:Role of insulin and glucagon in oxytocin effects on glucose metabolism. 134 36

To investigate the effects of alpha 2-adrenergic receptors on the secretions of pancreatic glucagon and insulin, clonidine, midaglizole and yohimbine were intravenously administered in four conscious sheep. Clonidine infusion at a dosage of 1.0 nmol/kg/min produced hyperglucagonemia, hypoinsulinemia and hyperglycemia. Midaglizole or yohimbine was infused for 30 min, at doses of 5, 10 and 50 nmol/kg/min during the clonidine infusion. The highest yohimbine infusion (50 nmol/kg/min) blocked the clonidine-induced responses of glucagon, insulin and glucose. On the other hand, the midaglizole (50 nmol/kg/min) infusion brought about no statistical effect on the clonidine-induced responses of glucagon, insulin and glucose. The alpha 2-adrenergic antagonistic effect of midaglizole was clearly less than that of yohimbine in the present experiments. It is concluded that the glucagon secretion is enhanced and the insulin release is inhibited by alpha 2-adrenergic stimulation in conscious sheep.
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PMID:Alpha 2-adrenergic modulation of glucagon and insulin secretions in sheep. 167 98

Pancreatic islets in anglerfish (AF) are macroscopic collections of nearly pure endocrine cells that are densely innervated. Immunohistochemical staining for neurotransmitter biosynthetic enzymes revealed noradrenergic and cholinergic innervation of AF islets. An in vitro preparation of perifused dispersed AF islet cells was developed to study nutrient and neural control of islet hormone secretion. Glucose stimulated insulin and somatostatin-14 (SS-14) secretion in a dose-dependent manner, and 16.7 mM glucose inhibited glucagon secretion. In 2 mM glucose, norepinephrine and isoproterenol stimulated glucagon and SS-14 release. Isoproterenol stimulated insulin secretion, and norepinephrine stimulated or inhibited insulin release, depending on the concentration. Clonidine potently inhibited glucose-stimulated insulin secretion but stimulated glucagon release. Methacholine, a muscarinic cholinergic agonist, stimulated insulin, glucagon, and SS-14 release. The control of AF hormone release by neurotransmitter agonists in vitro was similar to that in higher vertebrate species. Therefore we used this tissue preparation to study postsynaptic interactions between glucose and neurotransmitters in islets.
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PMID:Neuronal influence on hormone release from anglerfish islet cells. 168 34

It has been suggested that the increased activity of the sympathetic nervous system and the resultant increase in the tissue catecholamine levels contribute to the pathogenesis of diabetes. In this study we evaluated the effect of clonidine, a central adrenergic agonist that decreases sympathetic tone, on the serum levels of glucose, insulin, glucagon and norepinephrine and on the hepatic glycogen content in normal and streptozotocin-diabetic rats. The animals were treated with clonidine 25 micrograms/kg/day interperitoneally for 3 weeks to suppress the central adrenergic impulses. Clonidine treatment significantly increased the weight gain, but did not affect plasma glucose, insulin, glucagon and norepinephrine in the diabetic animals. Pancreatic insulin and liver glycogen contents were significantly higher in the clonidine-treated than in the untreated diabetic rats. However, clonidine did not affect pancreatic insulin and liver glycogen content of nondiabetic animals. The intravenous administration of glucagon increased plasma glucose in the clonidine-treated, but not in the saline-treated diabetic rats. Insulin-induced hypoglycemia significantly enhanced glucagon release in clonidine-treated but not in saline-treated diabetic rats. We conclude that the suppression of central adrenergic activity may ameliorate the effects of insulin insufficiency on pancreatic hormone secretion and hepatic glycogen content.
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PMID:Central adrenergic suppression augments the insulin and glucagon secretory, and the glycogenolytic responses in streptozotocin-diabetic rats. 181 6

In freshly collagenase-isolated rat pancreatic islets and in islets cultured for 72 hours, the effects of thiol reagents on glucagon (5 micrograms/ml) and/or glucose (16.7 mM)-mediated increases in cAMP formation as well as on clonidine (10 microM)-induced inhibition of these actions were studied. In freshly isolated islets and to a more pronounced degree in islets cultured for 72 hours glucagon (5 micrograms/ml) increased the cAMP content above the basal value. Clonidine (0.1-100 microM) had no significant effect on the basal cAMP formation, but inhibited the glucagon-mediated effect. The thiol reagents diamide (10-100 microM) and NEM affected neither the basal nor the glucagon-mediated effect, but abolished the inhibitory action of clonidine on cAMP formation. In freshly isolated islets, high glucose concentrations (8.3-16.7 mM) increased the cAMP formation. Diamide (100 microM) and NEM (100 microM) attenuated the stimulatory effect of 16.7 mM glucose. It is suggested that these selective effects of the thiol reagents on glucagon-mediated increase in cAMP formation in the presence of substimulatory concentration of glucose may be due to the differences in the sensitivity of the sulfhydryl groups of the G-proteins to thiol reagents i.e. Gi or proteins closely related to Gi being more sensitive than Gs. The data further suggest that glucose acts on the cAMP cascade at a step distinct from Rs. Since both glucose and glucagon effects were influenced by the addition of clonidine, it is possible to interpret the data as indicating that the effects of both stimulators eventually converge at some common step in the adenylate cyclase cascade.
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PMID:Thiol reagents (diamide and N-ethylmaleimide) inhibit increase in cAMP in response to glucose and abolish the clonidine-mediated attenuation of glucagon-induced cAMP formation in isolated rat pancreatic islets. 196 19

To evaluate whether clonidine exerts its action within the central nervous system or outside the central nervous system to induce hyperglycemia, we compared the effects of clonidine injected into the third cerebral ventricle or intravenously on hepatic venous plasma glucose concentrations in fasted rats. Clonidine administration produced a dose-dependent hyperglycemia in each case. At all tested doses (5, 50, and 100 nmol) the hyperglycemic responses to clonidine injected intravenously were not significantly different from those to clonidine injected into the third cerebral ventricle. Intraperitoneal pretreatment with yohimbine (50 nmol) or phentolamine (50 nmol), both alpha-adrenergic antagonists, reduced the hyperglycemic response to clonidine (100 nmol) given intravenously, but these antagonists preinjected into the third cerebral ventricle did not reduce the response. Moreover, no significant differences in venous plasma clonidine concentrations were observed when intravenous and third cerebral ventricle injections of clonidine (100 nmol) were compared. These results suggest that clonidine-induced hyperglycemia is mainly mediated by the peripheral mechanism rather than through the central mechanism. To gain an insight into the peripheral mechanism for the hyperglycemic action of clonidine, we measured the plasma immunoreactive glucagon and insulin concentrations after intravenous clonidine (100 nmol). We found that plasma immunoreactive glucagon concentrations significantly increased, whereas plasma immunoreactive insulin concentrations did not change significantly despite hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Central versus peripheral effect of clonidine on hepatic venous plasma glucose concentrations in fasted rats. 289 76

The aim of this study was to assess the acute effects of clonidine, an alpha 2-adrenergic agonist, on hormonal responses to graded exercise in 8 healthy young men. After fasting overnight, each subject was tested on 2 mornings, 1 week apart. On one occasion he was given 200 micrograms clonidine orally and on the other identical placebo tablets, the order being randomized in a double-blind fashion over the 2 days. Thereafter each subject performed 2 successive treadmill runs, equivalent to 60 and 100%, respectively, of maximal aerobic power. Clonidine pretreatment blunted the maximal increase in plasma catecholamines by more than 60% of the control response (p less than 0.01), without significantly altering the rise of plasma cortisol or ACTH. Furthermore, clonidine significantly reduced the exercise-induced maximal rise in plasma glucose, without modifying the slight decline in mean plasma insulin or increase in pancreatic glucagon levels. The drug did not affect the maximal increments in plasma growth hormone or prolactin occurring after exercise. It was concluded that a single dose of clonidine suppressed peripheral sympathetic responses, without altering central (pituitary) alpha-adrenergic-mediated hormonal responses, to short-term exercise in healthy men.
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PMID:Clonidine and the hormonal responses to graded exercise in healthy subjects. 300 52

Although originally devised to discriminate between patients with pheochromocytoma and those with elevated plasma catecholamine levels for other reasons, the clonidine suppression test has recently been used in patients with normal resting catecholamine levels. Upon review of 49 patients evaluated for pheochromocytoma, 26 had elevated plasma norepinephrine levels and underwent clonidine suppression testing. Only one of 13 patients with sustained elevated norepinephrine levels before clonidine administration had a false-positive clonidine test result, in contrast to five of 13 patients whose pre-clonidine norepinephrine levels had decreased into the normal range. This difference was statistically significant (by chi-square) at p less than 0.05. Clonidine suppression testing for pheochromocytoma should be performed only in patients with elevated catecholamine levels, because it carries a higher false-positive rate in patients with normal resting norepinephrine levels; a more accurate diagnosis may be made in such patients using glucagon stimulation tests.
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PMID:Reduced specificity of the clonidine suppression test in patients with normal plasma catecholamine levels. 334 44

Conflicting opinions were recently expressed concerning the possible effect of alpha 2-adrenergic agonists upon cyclic AMP production in pancreatic islets. In the present study, clonidine inhibited glucose-induced insulin release from rat pancreatic islets, this inhibitory effect being abolished by idazoxan. Clonidine did not suppress the capacity of forskolin to augment glucose-induced insulin release. In a particulate subcellular fraction derived from the islets, adenylate cyclase was activated by calmodulin (in the presence of Ca2+), NaF, GTP, L-arginine, and forskolin, and slightly inhibited by clonidine. The inhibitory action of clonidine upon basal adenylate cyclase activity was more pronounced in islet crude homogenates. The inhibitory effect of clonidine was antagonized by forskolin whether in the particulate fraction or crude homogenate. At variance with the modest effects of glucagon, D-glucose, L-arginine, or a tumor-promoting phorbol ester upon cyclic AMP production by intact islets, forskolin caused a six-fold increase in cyclic AMP production. Clonidine inhibited cyclic AMP production by intact islets, whether in the absence or presence of forskolin. It is proposed that the inhibitory action of clonidine upon insulin release is attributable, in part at least, to inhibition of adenylate cyclase.
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PMID:Inhibitory effect of clonidine upon adenylate cyclase activity, cyclic AMP production, and insulin release in rat pancreatic islets. 608 50

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


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