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 effect of hormones on cell volume was studied in isolated perfused rat liver by assessing the intracellular water space as the difference between a [3H]inulin- and a [14C]urea-accessible space. The intracellular water space (control value 559 +/- 7 microliters/g of liver; n = 88) increased on addition of insulin (35 nM) or phenylephrine (5 microM) by 12 or 8% respectively, whereas it decreased with cyclic AMP (cAMP; 50 microM), glucagon (100 nM) or adenosine (50 microM) by 9, 13 or 6% respectively. Both insulin and glucagon exerted half-maximal effects on cell volume and cellular K+ balance at hormone concentrations found physiologically in the portal vein. Adenosine-induced cell shrinkage was explained by a net K+ release from the liver. Phenylephrine (5 microM) led to cell swelling by about 8%, which was additive to insulin-induced swelling. Extracellular ATP (20 microM) induced cell shrinkage by about 6%; this was additive to adenosine-induced shrinkage. Vasopressin (15 nM) did not appreciably change cell volume, but induced marked cell shrinkage when glucagon or cAMP was present. Insulin- and phenylephrine-induced cell swelling was counteracted by cAMP. Hormone-induced changes of intracellular water space could sufficiently explain accompanying liver mass changes induced by glucagon, cAMP, adenosine or vasopressin, but not those by phenylephrine and extracellular ATP. The data show that liver cell volume is subject to hormonal regulation, in part owing to modification of cellular K+ balance. Glucagon- and insulin-induced cell volume changes occur already in the presence of physiological hormone concentrations. The effects of Ca2(+)-mobilizing hormones on cell volume are not uniform. In view of the recently established role of cell volume changes in modulating liver cell function, the present findings open a new perspective on the mechanisms of hormone action in liver, underlining our previous hypothesis that cell volume changes may represent a 'second messenger' of hormone action.
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PMID:Regulation of cell volume in the perfused rat liver by hormones. 166 Feb 61

To study the effect of glucagon neutralization on urea synthesis in diabetic rats, animals with newly induced (75 mg/kg streptozocin) experimental diabetes mellitus were divided into two groups. One group was given one weekly injection of nonimmune rabbit serum (n = 6), and the other group was given one weekly injection of a specific high-titer antibody against pancreatic glucagon (n = 6). Four weeks later, serum-treated diabetic rats had fasting glucagon concentrations 2-3 times higher than nondiabetic controls given one weekly injection of saline (control). Plasma glucagon binding capacity of diabetic rats given glucagon antibodies was 10-15 times higher than the glucagon concentration. A second group of nondiabetic controls were given nonimmune serum. Blood glucose concentration and urinary glucose output were identical in both groups of diabetic animals. Food intake doubled in both groups of diabetic rats. In control rats, the accumulated nitrogen balance, determined weekly for 4 wk, was positive at 81 +/- 3.1 mmol/96 h; in serum-treated diabetic rats, the accumulated nitrogen balance was negative, -8.3 +/- 2.4 mmol/96 h throughout the 4 wk, whereas it was higher at 4.7 +/- 2.3 mmol/96 h in the glucagon antibody-treated diabetic rats (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucagon immunoneutralization in diabetic rats normalizes urea synthesis and decreases nitrogen wasting. 172 32

Adrenalectomized and intact rats were given constant high-dose infusions of glucagon, 0.3 mg/kg per day for 7 days, with or without low-dose dexamethasone, 0.01 mg/kg daily, to test whether glucocorticoids potentiate glucagon induction of the 5 urea cycle enzymes as they do in cultured rat hepatocytes. Glucagon did not induce any of the urea cycle enzymes in adrenalectomized Sprague-Dawley rats and only induced argininosuccinate lyase (EC 4.3.2.1) in adrenalectomized inbred Wistar-Furth rats. Dexamethasone alone induced arginase in adrenalectomized and in intact Wistar-Furth rats and restored the other enzymes to normal levels in adrenalectomized rats. In intact Wistar-Furth rats, the combination of hormones gave synergistic increases of all 5 enzymes over the responses to each hormone alone, but in adrenalectomized rats the combination was only additive or less than additive compared with the sum of single hormone responses. The lack of synergism between the two hormones in adrenalectomized rats suggest that other factors play a role in glucagon induction of this cycle.
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PMID:Dexamethasone and glucagon cause synergistic increases of urea cycle enzyme activities in livers of normal but not adrenalectomized rats. 180 64

The effects of insulin and glucagon on liver cell volume and proteolysis were studied in isolated perfused rat liver. The rate of proteolysis was assessed as [3H]leucine release from single-pass-perfused livers from rats which had been prelabelled in vivo by intraperitoneal injection of [3H]leucine. The intracellular water space was determined from the wash-out profiles of simultaneously added [3H]inulin and [14C]urea. In normo-osmotic (305 mosM) control perfusions the intracellular water space was 548 +/- 10 microliters/g wet mass (n = 44) and was increased by 16.5 +/- 2.6% (n = 6), i.e. by 85 +/- 14 microliters/g, after hypoosmotic exposure (225 mosM). Glucagon (0.1 microM) decreased the intracellular water space by 17 +/- 4% (n = 4), whereas insulin (35 nM) increased the intracellular water space by 9.3 +/- 1.4% (n = 15). Also, in isolated rat hepatocyte suspensions insulin (100 nM) caused cell swelling by 10.7 +/- 1.8% (n = 16), which was fully reversed by glucagon. In perfused liver, insulin-induced cell swelling was accompanied by a hepatic net K+ uptake (4.5 +/- 0.2 mumol/g) and an inhibition of proteolysis by 21 +/- 2% (n = 12); further addition of glucagon led to a net K+ release of 3.8 +/- 0.2 mumol/g (n = 7) and fully reversed the insulin effects on both cell volume and proteolysis. Similarly, insulin-induced cell swelling and inhibition of proteolysis were completely antagonized by hyperosmotic (385 mosM) cell shrinkage. Furthermore, cell swelling and inhibition of proteolysis after hypo-osmotic exposure or amino acid addition were reversed by glucagon-induced cell shrinkage. There was a close relationship between the extent of cell swelling and the inhibition of proteolysis, regardless of whether cell volume was modified by insulin, glucagon or aniso-osmotic exposure. The data show that glucagon and insulin are potent modulators of liver cell volume, at least in part by alterations of cellular K+ balance, and that their opposing effects on hepatic proteolysis can largely be explained by opposing effects on cell volume. It is hypothesized that hormone-induced alterations of cell volume may represent an important, not yet recognized, mechanism mediating hormonal effects on metabolism.
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PMID:Regulation of liver cell volume and proteolysis by glucagon and insulin. 189 64

Achieving nitrogen accretion in patients with critical surgical illness or cancer cachexia is often not possible by the simple provision of calories and nitrogen. Cachexia may result from the metabolic derangements caused by release of inflammatory mediators such as tumor necrosis factor (TNF). We wished to determine whether recombinant human insulin-like growth factor I (rhIGF-I) preserves its protein-sparing effects in the face of high plasma TNF concentrations. Primed constant infusions of [15N]urea and [6-3H]glucose tracers were used to measure protein and glucose kinetics in fasted lambs. The lambs were divided into four groups: two groups received normal saline infusions of 480 min, and two groups received recombinant TNF (rTNF) infusions of 1 microgram.kg-1.h-1. During the last 300 min, one of the normal saline and one of the rTNF-infused groups were infused with rhIGF-I at a dose of 50 micrograms.kg-1.h-1. rTNF infusion resulted in the lambs becoming febrile and significantly increased plasma cortisol, glucagon, and insulin levels. rhIGF-I infusion in the control animals reduced the rate of loss of protein by 15% (P less than 0.01) and increased the rate of peripheral glucose clearance by 55% (P less than 0.01). rhIGF-I infusion in the rTNF-treated animals reduced the rate of net protein loss by 15% (P less than 0.01) and caused similar changes in glucose kinetics, as were observed in the control animals. We conclude that as rhIGF-I preserves its protein anabolic action in the face of high rTNF levels, further investigation into a possible clinical role for rhIGF-I in severe surgical illness is warranted.
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PMID:Effects of recombinant IGF-I on protein and glucose metabolism in rTNF-infused lambs. 195 85

Trauma and injury are associated with accelerated protein loss. Counterregulatory hormones are possible mediators of this response. In the present study, the effect of glucagon and glucagon plus bradykinin on leucine and urea kinetics was examined in nine normal volunteers during somatostatin infusion and basal insulin replacement. Bradykinin was given because of its prostaglandin-stimulating qualities and the potential anabolic action of prostaglandins. Physiological hyperglucagonemia elicited a small but significant reduction of total leucine flux and rate of urea synthesis. Simultaneously, leucine oxidation increased by 70%. The simultaneous infusion of bradykinin did not alter glucagon-related changes in urea or leucine kinetics. Bradykinin, however, significantly attenuated the stimulation of leucine oxidation by glucagon. These results suggest that glucagon and tissue factors are involved in controlling leucine metabolism in humans.
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PMID:Bradykinin attenuates glucagon-induced leucine oxidation in humans. 197 88

Metabolic changes in six severely affected tetanus patients suffering from characteristic labile hypertension (maximum systolic blood pressure greater than 200 mmHG, maximum diurnal change in systolic pressure greater than 100 mmHg) were investigated. Daily urinary excretion of urea nitrogen increased gradually from the onset of opisthotonus, reached a peak value (10.4 to 15.4 g/m2) in 8 to 20 days, and decreased subsequently. Average cumulative excretion in 30 days reached 239.6 +/- 32.7 g/m2. Urine catecholamine excretion was elevated in each patient and remained elevated during this period. Plasma cortisol and glucagon concentrations were not increased markedly except in a case complicated other systemic bacterial infection. Increased protein catabolism in these patients could not be explained by the metabolic effects of 'stressed hormones' alone, and neurologic factors must be considered.
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PMID:Metabolic changes in patients severely affected by tetanus. 198 40

The effects of i.v. glucagon-like peptide-1-(7-36)amide (GLP-1; 10 micrograms) on starved sheep given an i.v. glucose load (5 g) were studied. Plasma insulin concentrations rose significantly more after glucose administration in fed than in starved sheep. Giving GLP-1 to starved sheep increased the insulin response to the glucose load. The rise in plasma insulin concentrations in starved sheep given GLP-1 was similar to that observed in fed sheep. Plasma glucose concentrations returned to normal values more quickly in the starved sheep given GLP-1 than in starved sheep not given gut hormone. Plasma concentrations of free fatty acid, urea and alpha-amino nitrogen decreased more quickly following glucose administration in starved sheep given GLP-1 than in those not given GLP-1. The data suggest a role for GLP-1 in regulating plasma insulin concentrations and hence metabolism in ruminant animals. The possible role of gut hormones in ruminants is discussed.
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PMID:Effects of truncated glucagon-like peptide-1 on the responses of starved sheep to glucose. 203 Mar 30

In diabetes mellitus amino nitrogen is lost from organs and excreted as urea. Traditionally it has been assumed that the only explanation of this phenomenon was lack of insulin. The blood amino acid concentration in diabetic patients is, however, reduced, which suggests that the hepatic uptake of amino acids is accelerated. Glucagon accelerates the hepatic uptake and conversion of amino nitrogen into urea nitrogen, and hyperglucagonaemia is present in diabetes. This survey describes the significance of hyperglucagonaemia in the abnormal diabetic nitrogen metabolism. Rats with experimental diabetes and hyperglucagonaemia, given the same amount of food as controls, double the urinary excretion of urea-N within 4 days. This increase can be completely normalized by an intensive insulin treatment regimen, which normalises the hyperglucagonaemia as well. Selective hyperglucagonaemia in otherwise optimally insulin treated diabetic rats raises the urinary urea-N excretion by one third, also within 4 days. The kinetics of urea synthesis in experimental diabetes is changed towards an increased maximum rate, but only after 14 days, so this alone cannot explain the increased urea excretion. Constant hyperglucagonaemia increases the spontaneous rate of urea synthesis within 2 days. In uncontrolled diabetes nitrogen is lost from most organs, and most is lost from muscles. Selective hyperglucagonaemia in insulin treated diabetic rats leads to a loss of muscle nitrogen of about one third of that seen in uncontrolled diabetes. It is suggested that he glucagon induced loss of muscle nitrogen is due to an increased flux of amino nitrogen from muscle to liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Importance of glucagon for nitrogen loss in diabetes--via an accelerated hepatic conversion of amino nitrogen to urea nitrogen. 206 Mar 19

Six Holstein steers (313 +/- 10 kg BW) surgically fitted with hepatic portal, mesenteric venous, mesenteric arterial, and hepatic venous catheters were used in a replicated crossover design experiment to evaluate the feeding of Acremonium coenophialum-infected fescue hay on portal-drained visceral and hepatic nutrient metabolism. Only four steers had functional hepatic catheters. Infected (INF) and endophyte-free (EF) fescue hays were harvested on the same day in May, at the soft dough stage of maturity, from a similar location in southeast Kansas. The hay was chopped through a 2.5-cm screen and fed in 12 portions daily. Intake was limited to 5.2 kg of DM/d to equalize consumption. Each experimental period lasted 21 d. Dietary CP concentration was greater for INF than for EF (9.9 vs 8.6%); however, apparent digestibilities of DM (52.6%) and N (37%) were not different. Ruminal total VFA concentrations and molar proportions were not different with the exception of butyrate, which was increased (P less than .10) for steers when they were fed INF. Feeding of INF increased (P less than .05) arterial beta-hydroxybutyrate concentration and decreased (P less than .10) arterial butyrate concentration. Steers fed EF showed a greater (P less than .05) portal-arterial concentration difference for acetate and an increased (P less than .05) net portal flux of acetate (500 vs 620 mmol/h). No differences in net flux were noted for any of the other VFA, glucose, lactate, urea N, insulin, glucagon, or prolactin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of feeding endophyte-infected fescue hay on portal and hepatic nutrient flux in steers. 206 Dec 52


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