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)

A case of chronic secretory diarrhea with elevated plasma vasoactive intestinal peptide (VIP) and serum gastrin levels is described. Plasma secretin, glucagon, insulin, and cyclic adenosine and guanine monophosphate (cAMP and (CGMP) concentrations were normal. Administration of a prostaglandin synthetase inhibitor failed to decrease the volume of diarrhea. There was no evidence of laxative abuse, antral cell hyperplasia, gastric hypersecretion, or pancreatic hypersecretion. The pancreatic histology was interpreted as islet cell hyperplasia. Jejunal tissue cAMP and cGMP concentrations were in the same range as those obtained from three control subjects. This report suggests that cyclic nucleotides may not mediate intestinal secretion in hormone-induced diarrhea.
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PMID:Normal jejunal cyclic nucleotide content in a patient with secretory diarrhea. 21 Jul 31

1 Continuous recording of cardiac contractions and coronary flow from isolated perfused hearts of rats permitted the study of coronary reactions to: (a) cardiostimulation induced by single doses or slow infusions of noradrenaline, CaCl2, glucagon or electrically induced tachycardia; (b) short interruptions of coronary inflow (hypoxia). 2 Except during tachycardia the heart rate was kept constant at 210 beats/min by electrical pacing. 3 Metabolic coronary vasodilatation (MCD) resulting from cardiac hyperactivity induced by noradrenaline, Ca2+, tachycardia or glucagon was inhibited by administration of prostaglandin E2. Reactive hyperaemia response to hypoxia was unaffected by prostaglandin administration. 4 Inhibition of MCD could also be obtained by prolonged infusion with arachidonic acid (1.6 X 10(-7) M), presumably by its conversion into prostaglandin-like substance since arachidonic acid failed to block MCD in hearts from rats pretreated with non-steroidal anti-inflammatory drugs (indomethacin, naproxen, phenylbutazone). 5 Reactive hyperaemia was unaffected either by arachidonic acid or by blockade of the synthesis of prostaglandin-like substances by anti-inflammatory drugs. 6 Since prostaglandin synthetase inhibition does not prevent but may enhance MCD, we do not advocate prostaglandin-like substances as agents directly responsible for the coronary vasodilatation that follows cardiac hyperactivity. 7 We postulate that cardiac overproduction of prostaglandins may lead to a failure in the adaptive coronary flow response to cardiac hyperactivity (coronary insufficiency?).
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PMID:Myocardial synthesis of prostaglandin-like substances and coronary reactions to cardiostimulation and to hypoxia. 76 Aug 93

The circulatory response of the kidney to drugs is conditioned by a variety of factors, such as basal vascular tone, dietary sodium and structural changes in the renal vasculature which accompany aging and disease. In addition, any drug which affects systemic arterial pressure will activate renal autoregulatory processes, which are superimposed upon the direct effects of the drug on the renal circulation. Renal autoregulation in addition to passive pressure effects probably accounts for the relative constancy of renal blood flow during the administration of renal vasodilators such as nitroprusside, diazoxide and minoxidil. Renal vasodilators which have minor effects on systemic arterial pressure, such as dopamine and glucagon, increase renal blood flow. These effects have been employed clinically in low cardiac output states. A variety of drugs affect the renal circulation by modifying the effects of endogenous vasoactive substances. The mechanisms of action include: receptor blockade; ex, adrenergic and Ag II-mediated vasoconstriction: enhanced production by the administration of biochemical precursors; ex, arachidonic acid and I-dopa: inhibition of endogenous production; ex, prostaglandin synthetase inhibitors: and inhibition of breakdown of endogenous substances; ex, converting enzyme inhibition. The effect of each of these interventions will depend in part upon the rate of endogenous production of the relevant vasoactive material. The administration of diuretics affects renal blood flow in individually distinctive ways, the mechanisms of which have been only partially elucidated.
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PMID:Pharmacology of the renal circulation. 85 Nov 21

To determine glucogenic and hormonal responses in ruminants to indomethacin, a prostaglandin synthetase inhibitor, four lactating Toggenburg goats were used in a crossover design. Fifteen milligrams of indomethacin or 3 ml of saline were injected subcutaneously twice daily with propionate infused intrajugularly at a rate of 2 mM/min for 75 min as a challenge. Plasma glucose concentrations were increased by indomethacin injections. Plasma concentrations of insulin, glucagon, and 6-keto-prostaglandin F1 alpha were not affected by indomethacin injections. Propionate infusion elevated plasma glucose, insulin, and glucagon concentrations. A decreased insulin release in response to propionate challenge was observed with indomethacin injections.
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PMID:Effect of indomethacin administration on glucose homeostasis and pancreatic hormones in lactating goats. 266 42

Both glucagon and prostaglandin F2 alpha have been shown to stimulate a chloride-rich choleresis in dogs. This study was performed to ascertain the interrelationship between glucagon and prostaglandin F2 alpha in stimulating bile flow. The experiments were performed using dogs with chronic biliary and gastric fistulas. Initially, the effects of prostaglandin F2 alpha on serum glucagon levels were evaluated. Glucagon administration increased bile volume and chloride secretion as did prostaglandin F2 alpha. Serum glucagon levels during prostaglandin F2 alpha administration were increased significantly over baseline values. During prostaglandin F2 alpha administration, the increase in serum glucagon concentration correlated well with the increase in hepatic bile flow. Administration of somatostatin, a hormone known to inhibit glucagon release, prevented the choleresis produced by prostaglandin F2 alpha while simultaneously eliminating the hyperglucagonemia. Subsequently, the effects of glucagon on bile prostaglandin F secretion and the effect of prostaglandin synthetase inhibition on glucagon choleresis were evaluated. Bile prostaglandin F secretion increased from control values of 101 +/- 27 pg per min (mean +/- S.D.) during bile salt infusion alone to 1,498 +/- 1,086 pg per min during the administration of 1 microgram kg-1 hr-1 glucagon. The prostaglandin synthetase inhibitor, indomethacin, significantly decreased the choleresis, the increased bile chloride secretion and the increased bile prostaglandin F secretion produced by glucagon. The results of this study indicate that prostaglandin F2 alpha-stimulated bile flow is primarily the result of glucagon release and suggest that prostaglandin F2 alpha may be involved in glucagon secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The relationship between glucagon and prostaglandin F in stimulating canine hepatic bile flow. 345 73

We previously demonstrated that treatment with indomethacin in vivo significantly blunted the glucagon-induced glycemic response in the rat. This prostaglandin synthetase (cyclo-oxygenase) inhibitor also accentuated the evanescent effect of glucagon on hepatic glucose output in the intact, anesthetized rat. In this report, we present evidence that impairment of glucagon action in the rat liver by indomethacin is mediated through its inhibitory effect on both cAMP-dependent and cAMP-independent hepatic protein kinase. Indomethacin treatment did not have a measurable effect on any of the other components of the glucagon transducer system. Furthermore, infusion with glucagon for two hours that maintained plasma glucagon values at high physiological levels significantly reduced hepatic cAMP-dependent protein kinase activity without altering its Km. Glucagon infusion also down-regulated its own hepatic receptors and glucagon-stimulated cAMP production; prostaglandin E1-stimulated cAMP production was not affected. We concluded that prostaglandins may play a role in the regulation of hepatic protein kinases involved in the glucagon-stimulated glycogenolytic response and that glucagon-induced down-regulation extends at least to the hepatic protein kinases. However, a direct effect of indomethacin or protein kinase and the adenylate cyclase complex cannot be ruled out.
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PMID:Modulation of hepatic protein kinase activity by indomethacin. 608 43

We report a rare case of Bartter's syndrome in a 35-year-old woman with type 2 diabetes mellitus. The patient presented with leg weakness, fatigue, polyuria and polydipsia. Hypokalemia, metabolic alkalosis, and high renin and aldosterone concentrations were present, but the patient was normotensive. Gitelman's syndrome was excluded because of the presence of hypercalciuria, secondary hyperparathyroidism and bilateral nephrocalcinosis. The patients condition improved upon administration of a prostaglandin synthetase inhibitor (acemetacin), oral potassium chloride and potassium-sparing diuretics. Five months later, the patient discontinued acemetacin because of epigastric discomfort; at the same time, severe hypokalemia and hyperglycemia developed. Glucagon stimulation and water deprivation tests were performed. Type 2 diabetes mellitus with nephrogenic diabetes insipidus was diagnosed. To avoid further gastrointestinal complications, the patient was treated with celecoxib, a selective cyclooxygenase 2 inhibitor. This case serves as a reminder that Bartter's syndrome is associated with various metabolic derangements including nephrogenic diabetes insipidus, nephrocalcinosis and diabetes mellitus. When treating Bartter's syndrome, it is also prudent to remember that the long-term use of nonsteroidal anti-inflammatory drugs and potassium-sparing diuretics may result in serious adverse reactions.
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PMID:Bartter's syndrome with type 2 diabetes mellitus. 1925 37