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 site and rate of entry of insulin into the body may affect its metabolic actions. This study tested for the first time in man the hypothesis that the mode of action of endogenous insulin differs from peripherally injected insulin. In 11 nondiabetic and six diabetic patients we compared the effects on peripheral glucose utilization (PGU) and degree of hypoglycemia of the following: (1) glucagon-free insulin rapidly injected and slowly infused into the portal circulation via percutaneous splenic puncture; (2) peripheral intravenous inslin; (3) peripheral intravenous sodium tolbutamide. The arteriovenous glucose difference (A-V) and (A-V)/A ratios were calculated as parameters for measuring PGU. In nondiabetics our experiments showed: (1) similar magnitudes of hypoglycemia for insulin given by both routes, and (2) a significantly smaller (A-V)/A and therefore PGU, after the intraportal route, particularly after a slow infusion. Intravenous tolbutamide produced marked hypoglycemia and a small PGU comparable to that of slow intraportal infusion of insulin. In diabetics, results were similar. These findings suggest that, compared to the action of peripherally administered insulin, intraportally injected exogenous insulin or tolbutamide-induced endogenous insulin has a greater hepatic and a lesser peripheral effect on glucose metabolism.
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PMID:The physiologic significance of portal vs. peripheral injection of insulin in man. 113 Apr 34

Mongrel dogs were prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of modified Thomas cannulas into the duodenum and stomach. After recovery from surgery, experiments were performed by cannulation of the common bile duct for bile collection through the duodenal cannula. Bile flow and composition and the biliary clearance of erythritol were observed during secretin, glucagon, or sodium taurocholate choleresis and were compared with control studies. All test substances caused increased bile secretion. Sodium taurocholate caused a marked increase in bile salt output and in the biliary clearance of erythritol. Secretin caused a large increase in bile flow, no increase in bile salt output, and a very small increase in the biliary clearance of erythritol. The results indicate marked differences in the choleretic mechanism of sodium taurocholate and secretin and suggest that the principal action of taurocholate was on the canaliculi and the principal action of secretin was on the ducts.
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PMID:The choleretic mechanisms of sodium taurocholate, secretin, and glucagon. 114 27

Administration of 0.2 mg of glucagon by intravenous bolus resulted in an increase in plasma renin activity (PRA) in 2 of 5 normal volunteers on their usual diet. Two of the nonresponders subsequently showed a PRA response to glucagon after sodium depletion. A lower dose of glucagon (0.01 mg) had no effect on PRA despite a 31 mg/100 ml rise in blood glucose and peak plasma glucagon of over 2000 pg/ml. In conclusion, glucagon can stimulate PRA but it is not a potent stimulator; its effect may be potentiated by sodium depletion.
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PMID:Glucagon stimulation of plasma renin activity in humans. 115 Aug 61

The metabolic effects of glucagon and glucagon plus insulin on the isolated rat livers perfused with 10 mM sodium L-lactate as substrate were studied. Glucagon stimulated gluconeogenesis, ketogenesis and ureogenesis at the concentration used of 2.1 nM. The addition of insulin to give a glucagon-to-insulin ratio of 0.2 reversed all the glucagon effects. The glucagon enhancement of gluconeogenesis was accompanied by a rise in cytosolic and mitochondrial state of reduction of the NAD system and a fall in the [ATP]/[ADP] ratio. The analysis of the intermediary metabolite concentrations suggested, as possible sites of glucagon action, the steps between pyruvate and phosphoenolpyruvate as well as the reactions catalyzed by phosphofructokinase and/or fructose bisphosphatase. All the changes in metabolite contents were abolished when insulin was present. Glucagon increased the intramitochondrial concentration of all the metabolites, whose intracellular distribution was calculated. The finding of a significant rise in the calculated intramitochondrial concentration of oxaloacetate points to pyruvate carboxylation as an important site of glucagon interaction with the gluconeogenic pathway. A primary event in the glucagon action redistributing intracellular metabolites seems to be the mitochondrial entry of malate. The possibility is discussed that the changes in metabolite cellular distribution were brought about by the increased cellular state of reduction caused by the hormone.
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PMID:Glucagon and insulin control of gluconeogenesis in the perfused isolated rat liver. Effects on cellular metabolite distribution. 117 30

In experiments with rabbits, glucagon prolonged the half-period of absorption of sodium iodide 125J in the left ventricular myocardium. Regitine prevented acceleration of the heart rate and impairment of capillary flow after glucagon. In healthy rabbits hippurate 125J clearance was unaffected by glucagon. After injury of the heart muscle by injection of silver nitrate solution into the left ventricular wall and depression of blood pressure, glucagon partly normalized renal clearance of hippurate 125J.
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PMID:The influence of glucagon on the blood supply of the heart and kidneys in rabbits. 121 13

Twelve ileostomy patients were given subcutaneous SMS 201-995 therapy (100 micrograms t.d.s. for 5 days) in a randomized placebo-controlled trial. All patients had ileostomies constructed 60 cm proximal to the terminal ileum (proximal ileostomy) following restorative proctocolectomy. SMS 201-995 reduced the daily ileostomy output from 997 +/- 52 g to 736 +/- 28 g, P < 0.05, along with a decrease in daily sodium and chloride excretion (sodium: 92.60 +/- 8.51 to 75.22 +/- 8.64 mEq, chloride: 143.46 +/- 8.54 to 113.60 +/- 15.84 mEq; both P < 0.05). There were no significant changes in the plasma levels of glucagon, C peptide, insulin, renin or aldosterone with SMS 201-995 therapy. Patients developed no severe side effects and reported easier management of the ileostomy and a reduction in thirst. Our results suggest a possible clinical role for SMS 201-995 in the management of proximal ileostomy.
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PMID:Reduction of the effluent volume in high-output ileostomy patients by a somatostatin analogue, SMS 201-995. 129 41

The ligand-induced internalization of the hepatic glucagon receptor has been studied in rats in vivo using cell fractionation. Injection of glucagon (11 nmol/100 g BW) led to a 2- to 3-fold increase in glucagon-binding activity in Golgi-endosomal (GE) fractions along with a 10-20% decrease in binding activity in plasma membrane (PM) fractions. These changes were time and dose dependent, reaching a maximum by 12-24 min and undergoing reversal in 2 h. Glucagon injection also caused a 20% decrease in glucagon binding to the total particulate fraction, which did not occur when binding was measured in the presence of the detergent octylglucoside. The change in glucagon-binding activity in PM and GE fractions resulted mainly from a change in receptor number; affinity remained unaffected (apparent Kd, 0.5 and 5 nM, respectively). A 5- to 10-fold increase in the glucagon content of GE fractions was observed in glucagon-treated rats. Neither the distribution of PM and Golgi marker enzymes nor that of the asialoglycoprotein receptor was affected by glucagon treatment. Regardless of glucagon treatment, glucagon receptors in GE fractions were less sensitive to GTP than receptors in PM fractions with respect to both inhibition of steady state binding and dissociation of prebound ligand. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, glucagon-receptor complexes formed in PM and GE fractions and subsequently cross-linked showed the same apparent mol wt (57 kilodaltons). In addition, they were identically sensitive to N-glycanase treatment, with two major species of lower mol wt generated. However, only cross-linked complexes associated with PM fractions showed detectable GTP sensitivity. GE fractions displayed a GTP-sensitive adenylate cyclase activity that was about 12 times lower than that of PM fractions. In both fractions, activity was stimulated by the addition of forskolin (8-fold) and, to a lesser extent, glucagon (3-fold). In vivo glucagon treatment led to an increase in activity in GE, but not PM, fractions. These results are consistent with the view that upon acute occupancy, hepatic glucagon receptors are rapidly and specifically internalized along with their ligand. During this process, receptor retained structural integrity and uncouple, albeit partially, from other components of the adenylate cyclase system.
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PMID:Ligand-mediated internalization of glucagon receptors in intact rat liver. 131 25

Many studies suggest that smooth muscle relaxation caused by beta-adrenergic agents and various neuropeptides occurs as a result of an increase in cellular adenosine 3',5'-cyclic monophosphate (cAMP). However, the evidence is indirect, and furthermore does not demonstrate that an increase in cAMP is essential for mediating relaxation. To define more clearly the role of cAMP in receptor-mediated smooth muscle relaxation, we used a specific competitive antagonist of the action of cAMP on protein kinase A, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], and its S isomer, (S)-p-cAMPS, which functions as a cAMP agonist. In gastric smooth muscle cells from guinea pig, (S)-p-cAMPS caused a dose-related relaxation [50% inhibitory concentration (IC50) 86 +/- 59 nM]. Vasoactive intestinal peptide (VIP) produced smooth muscle cell relaxation (IC50 2.3 +/- 0.8 nM) through occupation of specific VIP receptors. (R)-p-cAMPS inhibited VIP-induced relaxation, with a rightward shift in the VIP dose-response curve, suggesting competitive antagonism. Furthermore, (R)-p-cAMPS inhibited relaxation induced by other agents that increase cellular cAMP (isoproterenol, calcitonin gene-related peptide, and glucagon) but not that induced by ATP or sodium nitroprusside. (R)-p-cAMPS had no effect on contraction stimulated by carbachol, cholecystokinin, or substance P. These data demonstrate that activation of protein kinase A is primarily responsible for mediating gastrin smooth muscle relaxation produced by adrenergic agents and various neuropeptides.
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PMID:A primary role for protein kinase A in smooth muscle relaxation induced by adrenergic agonists and neuropeptides. 132 27

Effects of androgen treatment of young female rats on glucagon- and catecholamine-sensitive adenylate cyclase activity and adrenergic receptors of hepatic membranes have been studied. Injections of testosterone propionate for 7 days showed a significant decrease in the adenylate cyclase activity responding to isoproterenol and glucagon. The decrease in hormonal stimulation of the enzyme was accompanied with the fall in activation by non-hormonal stimuli, such as forskolin, sodium fluoride, Gpp(NH)p and Mn, without any changes in the number and the affinity of beta-adrenergic receptors of the membrane. These results suggest that androgens exert post-receptor effects by inhibiting the activity of the catalytic unit of adenylate cyclase system in rat hepatic membranes.
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PMID:Effects of androgen treatment on adenylate cyclase system in rat hepatic membranes. 133 15

We have utilized canalicular (cLPM) and basolateral (blLPM) liver plasma membrane vesicles to investigate the domain localization of several Na(+)-dependent amino acid transporters. Neutral amino acid transport by systems N and ASC was measurable in both domains but was greater in blLPM vesicles. Sodium-dependent glutamate uptake (system X-) was preferentially localized to cLPM. The absolute activity and domain distribution of these three carriers remained unchanged after treatment of rats with a combination of glucagon and dexamethasone. A low level of basal system A activity was present in both the blLPM and cLPM. Glucagon-induced system A activity was first observed in blLPM vesicles approximately 60 min posthormone treatment and, in cLPM vesicles, approximately 30 min later. In situ perfusion of glucagon-treated rat liver with the membrane-impermeant protein modification reagent glutathione maleimide specifically inactivated blLPM system A activity and abolished the delayed arrival of hormone-induced activity to the cLPM. Transient perfusion of the liver with glutathione maleimide followed by a recovery period in vivo showed that the reagent did not irreversibly inactivate the transcytotic process and also provided an independent demonstration of the time delay between arrival of the carrier activity at the two membrane surfaces. These results support the concept of a transcytotic process in which the blLPM is the sorting site for the hormone-induced system A carrier proteins that eventually reach the cLPM.
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PMID:Plasma membrane domain localization and transcytosis of the glucagon-induced hepatic system A carrier. 133 91


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