Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amino acid and glucose metabolism was studied in nine awake 18-hour fasted dogs with chronic portal, arterial, and hepatic venous catheters before and for three hours after oral ingestion of amino acids. The meal was composed of a crystalline mixture of free amino acid, containing neither carbohydrate nor lipid. Following the amino acid meal, plasma glucose concentration declined slowly and this occurred despite a rise in hepatic glucose release. Portal plasma insulin rose transiently (30 +/- 7 to 50 +/- 11 microU/mL, P less than 0.05) while the increase in portal glucagon was more striking and persisted throughout the study (162 +/- 40 to 412 +/- 166 pg/mL). Over the three hours following amino acid ingestion, the entire ingested load of glycine, serine, phenylalanine, proline, and threonine was recovered in portal blood as was 80% of the ingested branched chain amino acids (BCAA). The subsequent uptake of these glucogenic amino acids by the liver was equivalent to the amount ingested, while hepatic removal of BCAA could account for disposal of 44% of the BCAA absorbed; the remainder was released by the splanchnic bed. During this time, ongoing gut production of alanine was observed and the liver removed 1,740 +/- 170 mumol/kg of alanine, which was twofold greater than combined gut output of absorbed and synthesized alanine. In the postcibal state, the total net flux of alanine and five other glucogenic amino acids from peripheral to splanchnic tissues (1,480 mumol/kg 3 h) exceeded the net movement of branched chain amino acids from splanchnic to peripheral tissues (590 mumol/kg/3 h).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Amino acid and glucose metabolism in the postabsorptive state and following amino acid ingestion in the dog. 373 11

The role of glucagon as a blood-borne mediator of the hyperdynamic circulation associated with chronic portal venous hypertension was assessed in the rat portal vein stenosis model. Selective removal of pancreatic glucagon from the circulation was achieved by intravenous infusion of a highly specific glucagon antiserum. Blood flow to splanchnic organs, kidneys, and testicles was measured with radioactive microspheres, and the reference-sample method. Glucagon antiserum had no effect on blood flow in the gastrointestinal tract of sham-operated (control) rats. However, the antiserum produced a significant reduction in hepatic arterial blood flow in the control rats, suggesting that glucagon contributes significantly to the basal tone of hepatic arterioles. In portal hypertensive rats glucagon antiserum significantly reduced blood flow to the stomach (22%), duodenum (25%), jejunum (24%), ileum (26%), cecum (27%), and colon (26%). Portal venous blood flow was reduced by approximately 30%. The results of this study support the hypothesis that glucagon mediates a portion of the splanchnic hyperemia associated with chronic portal hypertension.
 ...
PMID:Role of glucagon in splanchnic hyperemia of chronic portal hypertension. 377 72

Sheep were prepared with catheters in an artery and mesenteric, portal, and hepatic veins. Blood flows and metabolite concentration differences were measured across liver and gut. Net organ production rates were calculated for liver, portal drained viscera, and extrasplanchnic regions. Arterial glucose concentration rose for 2 h after endotoxin administration. The hyperglycemia was associated with increased hepatic glucose production. Hypoglycemia developed between 3 and 8 h when hepatic glucose production decreased closer to control values. Arterial glucagon concentrations rose to high levels during the hypoglycemic period. Neither hepatic blood flow or oxygen delivery limited glucose production; uptake of the gluconeogenic substrate lactate was reduced on some occasions. Glucose utilization was increased in shock. Portal glucose utilization accounted for 14.5% of nonhepatic glucose utilization. Increased portal glucose utilization was not related to plasma insulin concentrations or insufficient oxygen supply to the gut. Hyperglycemia drove glucose utilization. Although plasma insulin concentrations rose significantly in endotoxemia, the increase in pancreatic insulin output was much smaller and failed to attain statistical significance.
 ...
PMID:In vivo studies of hypoglycemia and lactic acidosis in endotoxic shock. 388 2

The concentrations of gut regulatory peptides were monitored simultaneously in the portal and arterial circulations of 8 healthy conscious swine in the fasted state and after a standard mixed meal. The sampling was achieved via chronic cannulations of these two vessels. Portal/arterial differences of insulin and glucagon were similar to those previously described, indicating the importance of hepatic extraction of these two hormones. Portal/arterial differences for the gastrointestinal regulatory peptides were relatively small, however, and the liver is unlikely to be of major importance in the metabolism of these peptides.
 ...
PMID:Effect of food on porcine gut regulatory peptides in arterial and portal venous blood. 407 36

To determine the effectiveness of glucagon suppression in improving glucose homeostasis in diabetes, tracer-determined glucose kinetics were measured during a 6-h somatostatin infusion in six alloxan-diabetic dogs (moderately severe diabetes) and five depancreatized dogs deprived of insulin treatment for 3 days (prolonged severe diabetes). Plasma immunoreactive glucagon (IRG) decreased 70 +/- 9% in the alloxan-diabetic and 80 +/- 4% in the depancreatized dogs. Portal vein levels of plasma immunoreactive insulin (IRI) fell (17.0 +/- 2.3 to 4 micro.5 +/- 0.4 microU/ml) as did peripheral vein IRI levels (6.7 +/- 0.9 to 4.7 +/- 0.5 microU/ml) in the alloxan-diabetic dogs. In the depancreatized dogs plasma IRI levels were undetectable. Plasma glucose concentrations fell (278 +/- 17 to 169 +/- 12 mg/dl) during IRG suppression in the alloxan-diabetic dogs due to a rapid and sustained decrease in glucose production (Ra) (6.0 + 0.9 to 3.6 + 0.3 mg X kg-1 X min-1). Glucose disappearance (Rd) decreased gradually (5.9 + 0.6 to 3.9 + 0.2 mg X kg-1 X min-1). In contrast, in the depancreatized dogs, IRG suppression did not alter glucose concentrations or kinetics. Thus, glucagon suppression decreased glycemia by decreasing Ra only in moderately severe diabetes. However, this was associated with decreased rather than improved glucose utilization. The ineffectiveness of glucagon suppression during prolonged severe diabetes could relate to the degree and duration of the metabolic derangement and/or indicate that the continuous presence of some insulin is necessary for glucagon suppression to improve glucose homeostasis.
 ...
PMID:Glucagon suppression improves glucoregulation in moderate but not chronic severe diabetes. 613 57

To assess the role of endogenous opiates on the hormonal and cardiovascular responses to moderate hemorrhage (H) and/or nociceptor activation, naloxone (Nx; 100 micrograms/kg, iv) was given coincident with H (10 ml/kg), tooth pulp nerve stimulation (TP), or H plus TP in anesthetized cats. We have previously reported that TP potentiated the ACTH response to H. Nx treatment did not affect this TP potentiation of ACTH after H, nor did Nx affect the ACTH response to H alone. This suggested that the interaction between nociceptor and baroreceptor afferent nerves, which may underlie the observed TP potentiation of ACTH release after H in the anesthetized cat, was not dependent upon naloxone-sensitive opiate pathways. In contrast, Nx attenuated the fall in arterial pressure during H or H plus TP and completely blocked the normally observed hyperglycemia. Catecholamines showed a prompt rise during H or H plus TP in Nx-treated animals. Thus, altered adrenomedullary hormone release cannot account for the attenuated fall in blood pressure or the inhibition of hyperglycemia during H or H plus TP. Nx presented alone or in combination with TP did not significantly affect any measured variable. To determine if Nx acted directly at the level of the liver to block H-induced hyperglycemia, a second group of animals received intraportal injections of Nx (20, 50, or 100 micrograms/kg) before H. Nx did not block the rise in glucose after H, although each of the three doses of Nx significantly attenuated the early (at +1 min) fall in blood pressure. Portal venous samples of glucagon and insulin during H were not significantly affected by Nx. These results suggest that 1) naloxone-sensitive endogenous opiate receptors are not necessary for the rise in ACTH during H or for the TP potentiation of H-induced increases in ACTH; 2) the fall in mean arterial pressure and the rise in glucose during H are selectively attenuated by Nx independent of significant changes in peripheral catecholamine levels when compared to Nx untreated animals; and 3) finally, Nx does not act directly at the liver to block the H-induced rise in glucose, but, rather, is effectively cleared from the circulation by the liver.
 ...
PMID:Selective opiate modulation of the physiological responses to hemorrhage in the cat. 631 22

Hepatocyte growth transition constants were measured during liver regeneration induced by 70% hepatectomy in portacaval shunted rats and in pair-fed sham-operated controls. Portal blood diversion 48 h before 70% hepatectomy coordinately reduced DNA synthetic and mitotic responses 60-70%. Both responses reflected preferential changes in overall rates of S- and M-phase entry (S delta and M delta, respectively); marked differences were not seen between experimental or control DNA synthesis and mitotic onset times (St = approximately 12 h; and Mt = approximately 20 h, for each group). Proliferative defects were manifested progressively across the liver lobule, from portal (approximately 44% of control) to midzonal (approximately 20%) to central areas (approximately 5%). In addition, radioautography and studies of [3H]thymidine uptake into nuclear DNA showed that in shunted rats, average DNA synthesis rates per hepatocyte fell 44-86% between 16-30 h. RIAs of glucagon and insulin in portal and aortic plasma obtained from 0-72 h showed overall reductions of 37-41% in hepatic hormone gradients of shunted rats. The greatest decreases occurred 8-24 h after 70% hepatectomy. Early (0-2 h) or late prereplicative (8-10 h) administration of insulin (0.02-1 mg kg-1) failed to restore [3H]thymidine uptake rates at 22-24 h to normal levels. However, exogenous glucagon (20 micrograms kg-1) given at 8-10 h increased these rates to 50% of control values. Higher doses (0.2-1 mg glucagon kg-1) were inhibitory. By contrast, no effects on DNA synthesis were found when glucagon was injected between 0-2 h. These findings suggest that hepatocyte growth transition constants are modulated selectively by different mitogens. Glucagon may control S delta and average hepatocellular DNA synthesis rates apart from other endocrine factors that regulate St.
 ...
PMID:Selective effects of portal blood diversion and glucagon on rat hepatocyte rates of S-phase entry and deoxyribonucleic acid synthesis. 633 1

In order to assess the interrelationships between stomach and pancreas regarding the secretions of somatostatin-like immunoreactivity (SLI), glucagon (IRG), and insulin (IRI), concentrations of the three hormones were assayed in portal plasma and portal blood flow was measured in enterectomized rats before and after the selective removal of stomach or pancreas. Portal plasma SLI, IRG, and IRI concentrations were significantly increased by i.v. arginine in control rats (pancreas + stomach present). After gastrectomy, SLI, IRG, and IRI concentrations were, respectively, 52 +/- 13% (N = 15; P less than 0.005), 234 +/- 40% (P less than 0.001), and 119 +/- 15% (NS) of the pregastrectomy values. A decreased SLI secretion, an increased IRG release, and an unmodified basal IRI release were estimated by portal flow measurement. The A- and B-cell responses to arginine in the gastrectomized rats were significantly higher than in the control rats, while the D-cell response was no longer detectable. After pancreatectomy, by contrast, SLI concentrations were 360 +/- 75% of the prepancreatectomy values (N = 12; P less than 0.001). This reflected an actual increment of SLI release, taking into account the concomitant measurement of portal blood flow. The concentrations of IRG declined by 51 +/- 5% (P less than 0.001) and IRI was no longer measurable. A- and B-cell responses to arginine also were no longer detectable. These results suggest that in these experimental conditions (1) the stomach restrained pancreatic A- and B-cell responses to arginine, perhaps through the SLI released from the stomach and (2) the pancreas restrained gastric SLI secretion, perhaps through insulin.
 ...
PMID:Reciprocal gastropancreatic modulations for the release of somatostatin-like immunoreactivity, glucagon, and insulin in the rat. 634 73

The effect of equal (1.1 +/- 0.1 g/kg body wt) amounts of glucose administered orally, or by peripheral intravenous or intraportal infusion on hepatic glucose uptake and fractional hepatic extraction of insulin and glucagon was studied in conscious dogs with chronically implanted Doppler flow probes on the portal vein and hepatic artery and catheters in the portal vein, hepatic vein, carotid artery, and superior mesenteric vein. Portal vein and hepatic vein plasma flow increased only after oral glucose administration. Arterial plasma glucose increased equally to 150-160 mg/100 ml after all three routes of glucose administration. Portal vein glucose was similar after oral (195 +/- 15 mg/100 ml) and intraportal glucose infusion (215 +/- 11 mg/100 ml) and significantly higher than after peripheral intravenous glucose. Hepatic glucose uptake after oral (68 +/- 4%) and intraportal glucose administration (65 +/- 7%) significantly exceeded that after peripheral intravenous glucose infusion (23 +/- 5%). The amount of insulin above basal presented to the liver during the 180 min after oral glucose was 7.6 +/- 1.3 U, 4.3 +/- 0.6 U after intraportal glucose, and 4.1 +/- 0.6 U after peripheral intravenous glucose. Hepatic extraction of insulin increased significantly after oral glucose (42 +/- 3 to 61 +/- 4%), but was unchanged after intraportal and peripheral intravenous glucose administration. When the portal vein glucose levels achieved during peripheral intravenous glucose infusion for 90 min were maintained by a subsequent 90-min intraportal glucose infusion, hepatic glucose uptake was significantly greater during the intraportal glucose infusion. Glucagon secretion was suppressed equally after oral glucose, intraportal glucose, and peripheral intravenous glucose administration; fractional hepatic extraction of that hormone, which was significantly less than that of insulin, was unchanged. These results indicate that hepatic glucose uptake is significantly greater after oral and intraportal glucose administration than after peripheral intravenous glucose infusion. This difference is not simply related to the amount of glucose or insulin presented to the liver and the increased hepatic glucose uptake did not depend solely upon the augmented fractional hepatic extraction of insulin. Hepatic extraction of insulin and hepatic glucose uptake appear to be regulated independently.
 ...
PMID:Differential effects of oral, peripheral intravenous, and intraportal glucose on hepatic glucose uptake and insulin and glucagon extraction in conscious dogs. 634 94

Effects of noradrenaline on the portal and aortic plasma pancreatic hormone concentrations were studied in the cold- and heat-acclimated rats in order to know possible roles of these hormones in temperature acclimation. Noradrenaline (NA) infusion (2 micrograms/min, i.v., 30 min) effected greater elevation of colonic temperature (Tc) in the cold-acclimated rats (CA) than in the warm controls (WC), and did not influence Tc in the heat-acclimated rats (HA) under hexobarbital anesthesia. Portal and aortic glucagon levels increased in the NA-infused CA and HA, but no changes were observed in the NA-infused WC. NA-infusion did not affect the portal and aortic insulin levels in WC and CA, but increased aortic insulin level in HA. Aortic glycerol and free fatty acid (FFA) levels increased in all NA-infused groups. Portal and jugular vein FFA levels increased in NA-infused WC, but did not in NA-infused CA and HA. Neither NA infusion, nor glucagon was related to the elevation of Tc in HA. These results suggest that temperature acclimation modifies a glucagon-releasing action of NA and the NA-released glucagon could cooperate with NA to enhance nonshivering thermogenesis in the cold.
 ...
PMID:Noradrenaline-induced secretions of pancreatic hormones in cold- and heat-acclimated rats. 636 8


<< Previous 1 2 3 4 5 6 7 8 Next >>