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)

Two chemically unrelated inhibitors of lipolysis were used in order to differentiate between the effect of FFA depression and a possible FFA-unrelated drug effect, respectively, on the plasma concentrations of GH, cortisol, and glucagon. Saline infusion served as a control experiment. In eight healthy male volunteers, a similar FFA depression by either iv infusion of nicotinic acid (3-pyridine-carboxylic acid, NA) or oral intake of an adenosine derivative, N(6)-allyl-N(6)-cyclohexyl-adenosine (AD-D), was followed by a significant GH increase (to 22.1 +/- 6.2 and 9.6 +/- 2.9 ng/ml at 240 and 270 min, respectively). Due to the large scatter of the GH concentrations during NA infusion, these responses were not significantly different. No GH increase occurred when the FFA depression was prevented by addition of a lipid infusion. In contrast, plasma cortisol and glucagon both increased significantly (by 107.4 micrograms/liter at 270 min and by 48.4 pg/ml at 60 min, respectively) during NA- but not during AD-D-induced FFA depression. Addition of the lipid infusion abolished the cortisol increase during NA infusion but had no influence on basal cortisol concentrations during AD-D intake. It lowered glucagon to values slightly below basal concentrations when added to the NA infusion and more markedly during AD-D administration. The results provide evidence that 1) depression of plasma FFA per se stimulates the secretion of GH, and 2) the increase of cortisol and glucagon during NA infusion is probably unrelated to the FFA depression. Hence, the stimulatory effect of FFA lack on glucagon secretion needs to be reconsidered.
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PMID:Growth hormone, cortisol, and glucagon concentrations during plasma free fatty acid depression: different effects of nicotinic acid and an adenosine derivative (BM 11.189). 634 70

Effects of glucagon and prostacyclin (PGI2) were studied in anesthetized dogs during sequential occlusive and postocclusive mesenteric ischemia induced by 90 min of tourniquet stenosis of the superior mesenteric artery (SMA). After 30 min of SMA stenosis, glucagon (1 microgram/kg/min, n = 7), PGI2 (30 ng/kg/min, n = 7), or saline (1 ml/min, n = 3) was infused intravenously for 30 min, followed by 30 min of continued ischemia. SMA flow and distal SMA pressure ( SMAP ) decreased 76% with SMA stenosis (P less than 0.01). Ileal wall flow measured by radiolabeled microspheres decreased from 45 to 13 ml/min/100 g (P less than 0.01); mesenteric AV O2 difference ( AVDO2 ) increased from 5.1 to 10.1 ml/dl (P less than 0.01); and mesenteric O2 consumption (VO2) decreased by 48% (P less than 0.05). Glucagon infusion caused a further decrease in ileal wall flow, to 10 ml/min/100 g (P less than 0.05), and an increase in AVDO2 to 11 ml/dl (P less than 0.05), despite a 22% increase in cardiac output. PGI2 caused a similar decrease in ileal wall flow and an increase in AVDO2 , although these were not statistically significant. Saline infusion caused no change in measured variables. In the second phase of this study, SMA blood flow was restored by tourniquet release. After animals had stabilized for 30 min, a repeat 30-min drug infusion was studied. In this postocclusive period, persistent gut ischemia was indicated by a reduction in VO2 to 76% of original baseline, associated with a 50% decrease in both CO and SMAQ . Intravenous infusion of glucagon at this time increased SMAQ by 195% (P less than 0.05) and resulted in a return of VO2 to its original baseline level. PGI2 infusion caused a 21% increase in SMAQ and a 16% decrease in AVDO2 (NS), but had no significant effect on VO2. Glucagon was effective in the management of postocclusive mesenteric ischemia but appeared to have a detrimental effect on ileal blood flow in severe occlusive ischemia.
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PMID:Effects of glucagon and prostacyclin in acute occlusive and postocclusive canine mesenteric ischemia. 637 91

Normal male rats were made hyperglycemic for 24 hours by the infusion of high amounts of glucose and the effect of mannose, glucose and glucose plus glucagon on insulin biosynthesis and release was studied in the isolated islets. Saline infused animals served as controls. It was found that all stimuli markedly enhanced the pro-/insulin biosynthesis in islets from hyperglycemic rats in comparison with saline infused animals. Maximal insulin release was observed in the control group with 300 mg/dl glucose plus 10 microgram/ml glucagon, while submaximal stimulation with 100 mg/dl mannose or glucose resulted in a higher insulin secretion rate in B-cells from hyperglycemic animals at 60 min, when compared with the saline infused animals. The results show that elevation of the blood glucose results in an overall stimulation of insulin biosynthesis and secretion, while lowering of the blood sugar as in starvation predominantly decreases the glucose dependent mechanisms for both insulin synthesis and release.
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PMID:Insulin biosynthesis and release in isolated islets from hyperglycemic male rats. 699 25

In more than half of 67 patients suspected of having pheochromocytoma, glucagon stimulation increased plasma free norepinephrine (NE) and epinephrine (E) 50% or more, with rising blood pressure or pulse rate; only three patients, however, harbored a pheochromocytoma. A low degree of catecholamine conjugation accounts for most of the false-positive results. In patients with low conjugated NE +E there was a greater rise in free NE +E and free E as well as in pulse rate after glucagon stimulation than in those with normal levels of conjugated NE+E. Glucagon-sensitive adenylate cyclase was found in pheochromocytomas but not in a functional adrenocortical adenomas. After sham administration of glucagon, there were rises in blood pressure but not in free NE or E in four patients. The glucagon-induced catecholamine test can be false-positive in hyperadrenergic essential hypertensive patients with abnormally low conjugated NE +E. Saline alone in a sham glucagon test in susceptible patients raises systolic blood pressure and pulse rate, and therefore, if plasma free NE and E are measured and found not to rise this type of false-positive result can be eliminated.
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PMID:Basis of false-positive glucagon tests for pheochromocytoma. 721 98

Blood-borne metabolic feedback vs. neural feedforward regulation of glucose homeostasis during exercise was investigated by infusion glucose and [3H]glucose for glucose appearance determination intravenously in rats running for 20 min at 28 m/min [approximately 85% of maximal O2 consumption (VO2max)]. Infused glucose corresponded to the exercise-induced increase in hepatic glucose production (HGP) found in saline-infused rats. Saline- and glucose-infused resting rats were also studied. Arterial blood was sampled for analyses of hormones and metabolites. Plasma epinephrine, norepinephrine, and insulin were always similar and HGP was initially similar in the two exercising groups, although glucose infusion resulted in higher plasma glucose compared with control (P < 0.05). Late during exercise, high plasma glucose (11.3 +/- 0.4 vs. 9.6 +/- 0.3 mM) and low glucagon (16 +/- 2 vs. 27 +/- 3 pM) in glucose- vs. saline-infused rats caused an inhibition of HGP in glucose-infused rats, although never below preexercise levels. In resting rats, glucose infusion resulted in elevated plasma glucose and insulin and, in turn, inhibition of HGP but had no effect on catecholamines, corticosterone, or glucagon. The findings indicate that during heavy exercise, glucose homeostasis is regulated primarily by neural feedforward mechanisms and that blood-borne metabolic feedback mechanisms play a regulatory role if metabolic error signals are pronounced.
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PMID:Effects of glucose infusion on hormone secretion and hepatic glucose production during heavy exercise. 828 74

The effect of lactate per se on alanine and glucose metabolism was studied in five overnight-fasted conscious dogs. Somatostatin was infused to inhibit endogenous pancreatic insulin and glucagon release and the hormones were replaced intraportally at basal rates. Saline (n = 5) or lactate (at 25 and 50 mumol.kg-1.min-1 for 90 minutes each) was infused, and blood samples were taken during the last 30 minutes of each 90-minute period. Insulin, epinephrine, norepinephrine, and cortisol levels remained unchanged during saline or lactate infusion. Glucagon level decreased slightly during lactate (94 +/- 7 to 74 +/- 9 and 79 +/- 8 pg/mL) and saline (91 +/- 8 to 90 +/- 4 and 81 +/- 11 pg/mL) infusions. There were no significant changes in lactate or alanine levels or net hepatic balances with saline infusion. Blood lactate level increased from 657 +/- 74 to 1,718 +/- 126 and 3,300 +/- 321 mumol/L (both P < .05) during the low- and high-lactate infusion periods, respectively. The liver produced lactate during the control (5.57 +/- 2.92 mumol.kg-1 x min-1) and low-lactate infusion (1.75 +/- 2.58 mumol.kg-1 x min-1) periods, but consumed lactate (3.89 +/- 3.31 mumol.kg-1 x min -1; P < .05) during the high-lactate infusion period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of lactate loading on alanine and glucose metabolism in the conscious dog. 847 11

To determine if insulin-like growth factor I (IGF-I) inhibits pulsatile growth hormone (GH) secretion in man, recombinant human IGF-I (rhIGF-I) was infused for 6 h at 10 micrograms.kg-1.h-1 during a euglycemic clamp in 10 normal men who were fasted for 32 h to enhance GH secretion. Saline alone was infused during an otherwise identical second admission as a control. As a result of rhIGF-I infusion, total and free IGF-I concentrations increased three- and fourfold, respectively. Mean GH concentrations fell from 6.3 +/- 1.6 to 0.59 +/- 0.07 micrograms/liter after 120 min. GH secretion rates, calculated by a deconvolution algorithm, decreased with a t 1/2 of 16.6 min and remained suppressed thereafter. Suppression of GH secretion rates occurred within 60 min when total and free IGF-I concentrations were 1.6-fold and 2-fold above baseline levels, respectively, and while glucose infusion rates were < 1 mumol.kg-1.min-1. During saline infusion, GH secretion rates remained elevated. Infusion of rhIGF-I decreased the mass of GH secreted per pulse by 84% (P < 0.01) and the number of detectable GH secretory pulses by 32% (P < 0.05). Plasma insulin and glucagon decreased to nearly undetectable levels after 60 min of rhIGF-I. Serum free fatty acids, beta-hydroxybutyrate, and acetoacetate were unaffected during the first 3 h of rhIGF-I but decreased thereafter to 52, 32, and 50% of levels observed during saline. We conclude that fasting-enhanced GH secretion is rapidly suppressed by a low-dose euglycemic infusion of rhIGF-I. This effect of rhIGF-I is likely mediated through IGF-I receptors independently of its insulin-like metabolic actions.
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PMID:A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans. 851 57

Postoperative hypoalbuminemia occurs frequently; however, the cause of this disorder is not clear. In a double-blind, placebo-controlled study we investigated to what extent hypoalbuminemia and protein catabolism are caused by counterregulatory stress hormones, which play an important role in the metabolic changes that follow surgery. We simulated the postoperative endocrine response in healthy volunteers with a cocktail of the counterregulatory hormones epinephrine, glucagon, and hydrocortisone. Saline was infused as a control in a second experiment. Serum albumin and stress hormone concentrations and nitrogen balance were measured for 34 h and were compared with published values for patients after abdominal surgery. Triple-hormone infusion mimicked the endocrine response after abdominal surgery adequately. It caused a negative nitrogen balance comparable with that after moderately severe surgery but no hypoalbuminemia (serum albumin < 35 g/L), although serum albumin was slightly reduced relative to the control group. No net nitrogen loss or hypoalbuminemia occurred after saline infusion. In conclusion, counterregulatory stress hormones do not cause hypoalbuminemia in healthy volunteers, but do produce protein catabolism.
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PMID:Differential effects of counterregulatory stress hormones on serum albumin concentrations and protein catabolism in healthy volunteers. 874 92

Quantitative determination of insulin secretion is of importance both clinically and in research. The optimal method has not been established, although several different methods have been used. We determined the reproducibility of islet function parameters obtained by the glucose-dependent arginine stimulation test, and also studied the priming effect of arginine on subsequent acute insulin responses. The test measures the acute insulin (AIR) and glucagon (AGR) responses to i.v. arginine (5 g injected over 45 s) at fasting glucose and glucose concentrations clamped at 14 and above 25 mmol/l, as well as the glucose potentiation of insulin secretion (slopeAIR) and the glucose inhibition of glucagon secretion (slopeAGR). When the test was performed twice in seven healthy women (mean +/- SD age 58.7 +/- 0.5 years, BMI 27.6 +/- 5.5 kg/m2), the AIRs to arginine had a within-subject coefficient of variation (CV) of 18.6% at fasting glucose, 18.7% at 14 mmol/l glucose and 16.3% at above 25 mmol/l glucose. The CVs for AGR were 11.6, 14.9 and 8.9%, respectively. The CV of the slopeAIR was 24% and of the slopeAGR 17.2%. The arginine priming study was performed in six healthy women (age 63.7 +/- 0.3 years, BMI 28.0 +/- 6.9 kg/m2). Saline or arginine (5 g) was injected at fasting glucose, followed by arginine (5 g) at 14 mmol/l glucose. There was no difference between the acute insulin or glucagon responses to arginine at 14 mmol/l glucose in the two conditions, suggesting that there is no priming effect of arginine on the subsequent acute insulin or glucagon responses. Therefore, this method is a good tool to determine insulin secretion as, apart from its good reproducibility, it also provides several important parameters of islet function.
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PMID:Glucose-dependent arginine stimulation test for characterization of islet function: studies on reproducibility and priming effect of arginine. 968 17

Peripheral vasodilation initiates the hyperdynamic circulation in cirrhosis. Somatostatin and its analogues, such as octreotide, have a vasoconstrictive effect in cirrhotic patients and experimental animals with portal hypertension. The exact mechanism of octreotide-induced vasoconstriction remains unknown. To investigate whether octreotide produces vasoconstriction through suppression of vasodilatory peptides, such as glucagon, or through a local effect, we evaluated the effect of an intra-arterial dose on forearm blood flow (FBF), while measuring systemic glucagon levels. FBF was measured in 10 cirrhotic patients by venous occlusion plethysmography. The brachial artery of the nondominant arm was catheterized, and vasoactive drugs were administered: methacholine 4 microg/min; octreotide 20 microg/h, and octreotide 20 microg/h + methacholine 4 microg/min. Each infusion, lasting 5 minutes, was followed by saline for washout. FBF was measured in both arms during the last minute of each infusion and at the end of washout, with the uninfused arm acting as the control. Nitrates and nitrites, octreotide, and glucagon blood levels were determined at baseline and after each infusion. Percent change in flow (%triangle up) was obtained by comparing the flow during drug administration to that during the preceding saline infusion. Saline infusion did not alter FBF, but octreotide infusion resulted in a 34% +/- 7.7 (P <.005) reduction in FBF in the infused arm. FBF in the control arm was unchanged despite a significant decrease in systemic glucagon levels. Methacholine infusion increased FBF around 300%, which was not altered by the concomitant infusion of octreotide. Octreotide has a local vasoconstrictive effect that seems nitric oxide (NO)-independent. Octreotide probably has a facilitating effect over vasoconstrictors increased in chronic liver diseases.
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PMID:Local arterial vasoconstriction induced by octreotide in patients with cirrhosis. 1070 44


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