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)

Four calves (avg wt 161 kg) were surgically fitted with indwelling catheters in the femoral artery and femoral, portal, hepatic and mesenteric veins to study the effects of subclinical ammonia toxicity on portal-drained viscera (PDV) and hepatic (HEP) net flux of key metabolites and pancreatic hormones. Hyperammonemia was induced via administration of ammonium chloride (NH4Cl; 12 mumol.kg BW-1.min-1) via the femoral vein catheter for 240 min; infusions were preceded (PRE) and followed (POST) by 60- and 180-min control periods, respectively. Blood samples were obtained from the arterial catheters, and portal and hepatic vein catheters. Net flux rates were calculated by multiplying venoarterial differences by blood flow. Arterial plasma ammonia N peaked (P less than .01) at 327 micrograms/dl; hepatic ammonia extraction increased (P less than .01) from 10 to 23% during NH4Cl infusion. Arterial plasma glucose concentrations increased (P less than .05) during NH4Cl infusion (90.5 vs 82.6 mg/dl) concomitant with trends toward a reduction in net HEP glucose output. Portal-drained visceral release of insulin did not increase (P greater than .10) during NH4Cl infusion despite the steady rise in circulating glucose concentration; however, cessation of NH4Cl infusion resulted in a 109% increase (P less than .05) in PDV insulin release at +60 min POST. Plasma L-lactate, nonesterified fatty acids, urea N and glucagon concentrations and net fluxes were variable throughout the experiment. Results tend to indicate that hyperammonemia reduced hepatic glucose output and glucose-mediated pancreatic insulin release.
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PMID:Subclinical ammonia toxicity in steers: effects on hepatic and portal-drained visceral flux of metabolites and regulatory hormones. 220 Jul 75

A gastric [U-14C]glucose load (4.8 mg/g body wt.) was delivered to unrestrained post-absorptive or 30 h-starved rats bearing peripheral and portal vein catheters and continuously perfused with [3-3H]glucose, in order to compare their metabolic and hormonal responses. In the basal state, portal and peripheral glycaemia were less in starved rats than in rats in the post-absorptive period (P less than 0.01), whereas blood lactate was similar. Portal insulinaemia (P less than 0.05) and protal glucagonaemia (P less than 0.005) were lower in starved rats, but insulin/glucagon ratio was higher in post-absorptive rats (P less than 0.005). The glucose turnover rate was decreased by starvation (P less than 0.005). After glucose ingestion, blood glucose was similar in post-absorptive and starved rats. A large portoperipheral gradient of lactate appeared in starved rats. Portal insulinaemia reached a peak at 9 min, and was respectively 454 +/- 68 and 740 +/- 65 mu-units/ml in starved and post-absorptive rats. Portal glucagonaemia remained stable, but was higher in post-absorptive rats (P less than 0.05). At 60 min after the gastric glucose load, 30% of the glucose was delivered at the periphery in both groups. The total glucose appearance rate was higher in starved rats (P less than 0.05), as was the glucose utilization rate (P less than 0.05), whereas the rate of appearance of exogenous glucose was similar. This was due to a non-suppressed hepatic glucose production in the starved rats, whereas it was totally suppressed in post-absorptive rats. At 1 h after the glucose load, the increase in both liver and muscle glycogen concentration was greater in starved rats. Thus short-term fasting induces an increased portal lactate concentration after a glucose load, and produces a state of liver insulin unresponsiveness for glucose production, whereas the sensitivity of peripheral tissues for glucose utilization is unchanged or even increased. This might allow preferential replenishment of the peripheral stores of glycogen.
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PMID:Initial glucose kinetics and hormonal response to a gastric glucose load in unrestrained post-absorptive and starved rats. 220 4

Portal-systemic blood shunting is often accompanied by hyperglucagonemia and hemodynamic changes. To determine this causal relation, splanchnic and systemic hemodynamics (radioactive microspheres) and plasma glucagon levels (radioimmunoassay) were assessed in conditions of total portal-systemic shunting in portacaval-shunted (PCS) rats and in sham-operated (SO) normal rats. To compare these results, another hemodynamic study was undertaken basally and during glucagon infusion in nonoperated normal rats. PCS rats showed a threefold greater plasma glucagon concentration than SO animals (924 +/- 134 vs. 309 +/- 18 pg/ml, p less than 0.01), and they developed a hyperdynamic splanchnic circulation with higher portal venous inflow than SO rats (8.29 +/- 1.1 vs. 5.09 +/- 0.4 ml/min/100 g, p less than 0.05). Infusion of a pharmacological dose of glucagon in normal rats increased portal venous inflow (from 4.92 +/- 0.33 to 6.24 +/- 0.48 ml/min/100 g, p less than 0.05) so as to imply this hormone in the development of the hyperdynamic splanchnic circulation in conditions of portal-systemic shunting. However, the discrepancies in systemic hemodynamics between PCS and glucagon-infused rats may be a result of the different plasma glucagon levels reached in the two groups.
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PMID:Role of glucagon in the splanchnic and systemic hemodynamic changes induced by portal-systemic blood shunting. 222 22

This study examined whether hyperglucagonism may promote an altered sensitivity to norepinephrine (NE) and contribute to systemic vasodilation in rats with portal hypertension due to portal vein stenosis. Three groups of male Sprague-Dawley rats were studied, portal hypertensive, normal controls, and hyperglucagonemic controls. Systemic vascular reactivity was studied by constructing dose-response curves of systemic vascular resistance (SVR) during infusions of increasing doses of NE and calculating NE ED50, the dose of NE that caused 50% of the maximal increase in SVR. Measurement of SVR was based on simultaneous measurements of arterial pressure and cardiac output (CO). Repeated measurements of CO were performed by indicator dilution curves of indocyanine green by means of a fiber-optic catheter placed in the carotid artery. Portal hypertensive rats had a decreased systemic sensitivity to NE, shown by a significant increase in NE ED50 compared with normal controls (60 +/- 8 micrograms vs. 25 +/- 3 micrograms; P less than 0.001). Glucagon levels were markedly increased in the portal hypertensive group (332 +/- 51 pg/ml vs. 176 +/- 22 pg/ml in controls; P less than 0.005). Glucagon infusion in normal rats achieved levels similar to those observed in portal hypertension (305 +/- 48 pg/ml; NS). Systemic vascular sensitivity to NE was also impaired in these hyperglucagonemic normal animals, as shown by an abnormal NE ED50 (69 +/- 16 micrograms; P less than 0.001 vs. controls) that was almost identical to that observed in portal hypertension. These results are consistent with the hypothesis that a reduced sensitivity to NE can contribute to systemic vasodilation in portal hypertension and suggest that hyperglucagonism can play a key role in its pathogenesis.
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PMID:Decreased systemic vascular sensitivity to norepinephrine in portal hypertensive rats: role of hyperglucagonism. 230 84

The intestinal metabolism of glucose and glutamine was studied in rats made septic by cecal ligation and puncture technique. Sepsis resulted in negative nitrogen balance and produced increases in the concentrations of blood pyruvate, lactate, alanine, and glutamine, and decreases in those of 3-hydroxybutyrate and acetoacetate. Both plasma insulin and glucagon concentrations were increased by 2.2- and 3.2-fold in septic rats, respectively. Portal-drained visceral blood flow increased in septic rats, and was accompanied by a decrease in the rates of utilization of glutamine and production of lactate, glutamate, and ammonia compared with those rates in sham-operated animals. Enterocytes isolated from septic rats showed decreased rates of glucose and glutamine utilization compared with cells isolated from corresponding controls. The maximal activities of hexokinase, 6-phosphofructokinase, pyruvate kinase, and glutaminase were decreased in intestinal mucosal scrapings of septic rats. It is concluded that a moderate form of sepsis decreases the rates of glucose and glutamine utilization (both in vivo and in vitro) by the epithelial cells of the small intestine. This may be caused by changes in the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells as a metabolic adaptation to spare glucose and glutamine for use by other tissues.
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PMID:Glucose and glutamine metabolism in the small intestine of septic rats. 236 28

In this study, side-to-side mesocaval shunt (MCS-SS), pericardial devascularization (PCDV), and combined operation of the two procedures were performed in 3 groups of thioacetamide induced liver cirrhotic of rats. Portal and hepatic hemodynamics were investigated on a period of six weeks postoperation, and glucagon concentration in portal vein (PV) and inferior vena cava (IVC) was measured before and six weeks after the surgery. It was found that following PCDV, free portal pressure (FPP) was initially elevated without an increase of total hepatic blood flow (THBF) within four weeks, then both FPP and THBF were shown to decrease on the sixth week. After MCS-SS with a stoma diameter of 2.0mm, a 31% decrease of FPP (P less than 0.05) and a 23% decrease of THBF (P less than 0.05) were observed, though the portal blood flow remained hepatopetal and hyperglucagonemia in PV was not changed. After combined procedure there was a greater decrease of FPP and THBF than that after MCS-SS, and the concentration of glucagon in PV was decreased without any change of its content in IVC.
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PMID:[Effects of side-to-side mesocaval shunt, pericardial devascularization, and a combined procedure in cirrhotic rats]. 237 25

The effect of hepatectomy and administration of glucagon on hepatic hemodynamics were studied using mongrel dogs. The results were as follows: 1) Hepatic blood flow in the 70% hepatectomized dogs was significantly less than that in dogs subjected to sham operation or 40% hepatectomy. 2) Bolus injection of glucagon (10 micrograms/kg) increased blood flow in the hepatectomized dogs as well as that in the control dogs. The percentage increment, however, was significantly smaller in the 70% hepatectomized dogs, possibly due to little increase of portal vein blood flow. 3) Portal vein pressure and its resistance were significantly higher in the 70% hepatectomized dogs than in both the 40% hepatectomized dogs and the control dogs. 4) Although pre-sinusoidal resistance showed no significant difference among these three groups, post-sinusoidal resistance increased stepwise in the order of extent of hepatectomy. These results suggest that administration of glucagon after extended major hepatectomy is not so particularly effective in generating adequate hepatic tissue blood flow.
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PMID:[Hepatic hemodynamics after hepatectomy and the effect of administration of glucagon]. 238 22

Somatostatin is an inhibitory hormone that decreases the secretion and end organ response of cholecystokinin (CCK). Inhibition of hormonal stimulation of pancreatic exocrine secretion by somatostatin may improve the course of acute pancreatitis. Anesthetized dogs underwent cholecystectomy and cannulation of the pancreatic duct, thoracic duct, and portal vein. Twenty experiments were performed in random order with 5 dogs in each group. Hourly measurements of lymph flow and portal and thoracic duct amylase were made. Portal blood insulin, glucagon, and CCK concentrations were determined by radioimmunoassay on samples obtained at the beginning and end of the experiments. Pancreatitis was induced by injecting, under constant pressure, 10 ml bile into the pancreatic duct during 1 min. Somatostatin was administered intravenously (20 micrograms/kg/hr). After 5 h, the dogs were killed, pancreas glands removed and weighed and tissue samples obtained for histologic evaluation. There was a significant increase in lymph amylase output and portal venous amylase and CCK concentrations in the dogs with pancreatitis compared to the control dogs. In dogs with pancreatitis, lymphatic amylase secretion and portal CCK concentrations were significantly decreased by somatostatin. Somatostatin did not significantly alter portal amylase concentrations, pancreas gland weights or histologic inflammation when compared to values from dogs with pancreatitis not treated with somatostatin.
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PMID:Effects of somatostatin on acute canine experimental pancreatitis. 244 77

Glucagon, in the anesthetized cat, was capable of dilating the hepatic artery to the same extent and in a dose-dependent manner when administered directly into the hepatic artery or into the portal vein. Portal venous infusions of glucagon did not inhibit nerve- or norepinephrine-induced vasoconstriction of the hepatic artery in contrast to previous reports in the dog. Rather, at certain doses, glucagon mildly potentiated the vasoconstriction induced by both constrictor stimuli. Vascular escape from nerve- and norepinephrine-induced constrictor responses was found to be inhibited by glucagon in a dose-dependent manner. Glucagon infusion is the first intervention reported to modulate vascular escape in the hepatic artery. Owing to its similar effects on nerve- and exogenous norepinephrine-induced responses, glucagon appears to be acting at a postsynaptic site. Therefore, we suggest that in the cat, glucagon is not an inhibitory modulator of nerve- and norepinephrine-induced vasoconstriction, but rather may potentiate the constrictor response in a postsynaptic manner.
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PMID:The effect of glucagon on vasoconstriction and vascular escape from nerve- and norepinephrine-induced constriction of the hepatic artery of the cat. 262 82

Comparative measurements of portal vein blood flow were performed at laparatomy in anesthetized dogs using either a pulsed Doppler echo system or electromagnetic flowmeters. Three hundred four simultaneous determinations were obtained under baseline conditions and during vasopressin and glucagon infusions. In each dog, serial triplicate measurements were taken within 10 min of each other. In all the cases, flow changes induced by vasoactive drugs followed the same direction regardless of the method used. Portal vein blood flow as measured by electromagnetic flowmetry ranged from 85 to 1570 ml/min. Portal vein blood flow values obtained with Doppler and electromagnetic flowmeters were not significantly different (609 +/- 335 vs. 600 +/- 370 ml/min; p = NS) and were highly correlated (r = 0.918, p less than 0.001). The difference between values obtained by the two techniques was -3 +/- 159 ml/min or -1.0% +/- 21.2% (mean +/- SD). This difference was not influenced by the portal vein diameter but increased slightly as a function of the angle of insonation. When considering the mean of triplicate measurements, we also found a highly significant correlation between data obtained by the two techniques (r = 0.934, p less than 0.001; n = 63). The mean difference was 11 ml/min, but limits of agreement between these methods were -267 and +239 ml/min. This relative discrepancy was explained by a coefficient of variation higher in Doppler measurements than in electromagnetic measurements (10.9% vs. 5.9%). These data demonstrate that under our experimental conditions, Doppler flowmetry is probably not an ideal method to measure absolute portal vein blood flow values, and that more sophisticated equipment is needed to improve its reproducibility and accuracy. In humans, however, this method might be a useful tool to assess the direction of portal flow changes in the same individual.
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PMID:Portal vein blood flow measurements using pulsed Doppler and electromagnetic flowmetry in dogs: a comparative study. 264 55


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