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)

In order to assess the role of glucagon in human protein metabolism and to examine its action as a "catabolic" hormone, studies were conducted in two normal male subjects over an 8-day period. After minimum and stable urinary nitrogen excretion had been produced by the continuous nasogastric administration of carbohydrate (720 g/day) for 8 consecutive days, a continuous intravenous infusion of glucagon (1.0 mg/24 hr) was superimposed on days 7 and 8. Excretion of total nitrogen (N) and urea-N increased significantly (p less than 0.05). Excretion of 3-methylhistidine was unaltered, suggesting that the source of the N losses produced by glucagon did not derive from increased muscle proteolysis. Although striking hypoaminoacidemia was produced, the reductions of extracellular amino acids alone could not account for all of the extra urea excreted. These data suggest that hyperglucagonemia in normal man induces mild nitrogen losses by stimulation of hepatic ureogenesis from free intracellular amino acid pools and not by increased rates of muscle protein breakdown.
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PMID:Glucagon infusion in normal man: effects on 3-methylhistidine excretion and plasma amino acids. 40 91

Because in the dog, the gastric fundus contains the largest amount of glucagon immunoreactivity (IRG), the IRG of mucosal scrapes of 105 canine stomachs was extracted by acid-ethanol and then precipitated by ether-ethanol. The IRG recovered was measured by antisera 30K, specific for glucagon and K-4023, which cross-reacts with glucagon-like immunoreactivity. Extracts of mucosa of stomach fundus were further purified by gel filtration on Bio-Gel P-30 in 3M acetic acid. One pooled fraction corresponding to marker pancreatic glucagon in its elution volume was then gel-filtered on Bio-Gel P-30 in 0.05 M NH(4)HCO(3) and yielded one IRG peak, which, however, showed three immunoreactive components on polyacrylamide disc gel electrophoresis in urea. In addition, antiserum K-4023 reacted more strongly with that peak than antiserum 30K indicating the presence of glucagon-like immunoreactivity in this fraction. Subsequent ion-exchange column chromatography on DEAE-Sephadex A-25 and then CM-Bio-Gel A allowed purification to a single protein band on disc gel electrophoresis reacting equally to both antisera 30K and K-4023. 1.5 mug of purified gastric glucagon was obtained and its biological effects were compared to those of pancreatic glucagon in isolated rat hepatocytes. When immuno-equivalent amounts (300-2,500 pg/ml) of either type of glucagon were used, the same biological responses with respect to glycogenolysis and gluconeogenesis as well as urea, lactate, and pyruvate production were observed. Liver cyclic AMP was also raised to the same extent by either one of these hormones. We conclude that this moiety of gastric IRG is apparently identical to pancreatic glucagon because (a) their molecular weights, elution properties in ion exchange chromatography, and their electrophoretic mobility are indistinguishable and (b) both hormones elicited identical biological effects in isolated rat hepatocytes.
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PMID:Identical biological effects of pancreatic glucagon and a purified moiety of canine gastric immunoreactive glucagon. 42 72

Glucagon immunoreactivity (IRG) was measured in plasma of 8 duodenopancreatectomized patients with antiserum 30-K. Arginine infusions failed to raise plasma IRG, whereas in control subjects IRG rose 3-fold. Column chromatography revealed that the basal IRG measured in these plasmas was not due to glucagon (molecular weight 3485) but to other plasma factors, mainly of high molecular weight. This suggests that diabetes mellitus does not require the presence of glucagon to produce the clinical picture, as suggested by other authors. Plasma levels of the amino acids alanine, serine, ornithine, and arginine were significantly (p less than 0.05) elevated, the former two being gluconeogenic substrates and the latter two constituents of the urea cycle. This amino acid abnormality may be a consequence of glucagon deficiency.
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PMID:[Fractional distribution of anti-glucagon immunoreactivity (GIR) and amino acid concentration in the plasma in duodenopancreatectomized patients; preliminary report]. 43 89

Glucogon immunoreactivity (IRG) was measured in plasma of duodenopancreatectomized subjects with a nonspecific (K-4023) and a specific (30-K) glucagon antiserum. After an overnight fast, plasma IRG (K-4023) was significantly (P < 0.05) higher in the subjects without pancreas, averaging 782+/-79 (SEM) pgeq/ml, than in the controls (482+/-80 pgeq/ml). IRG (30-K) of 162+/-68 pg/ml did not change during an infusion of arginine (450 mg/kg per 40 min). Insulin deprivation during 3 d in one patient did not restore the IRG response to arginine as reported in depancreatized dogs.Bio-Gel P-30 column chromatography revealed that virtually all IRG (30-K) measured in whole plasma was of different molecular weight than glucagon, and primarily of a mol wt >/= 40,000. Intravenous arginine did not significantly alter the chromatographic pattern of these plasmas. Thus, as postulated by others, duodeno-pancreatectomized humans have virtually no circulating 3,500-dalton glucagon. Hence, the presence of 3,500-dalton glucagon in plasma is not a condition for the diabetic state. It might, nevertheless, when present in normal or excessive amounts, worsen the metabolic state of diabetic patients. Among 14 amino acids measured in plasma of these patients, the concentrations of alanine, serine, ornithine, and arginine were significantly (P < 0.05) elevated to approximately twice that of normal: alanine and serine are both substrates for gluconeogenesis, whereas ornithine and arginine are involved in the formation of urea, the second product of hepatic gluconeogenesis. As the concentrations of branched chain amino acids were not grossly altered, it is hypothesized that this amino acid pattern is a consequence of glucagon deficiency rather than secondary to the diabetic state of these patients.
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PMID:Glucagon immunoreactivities and amino acid profile in plasma of duodenopancreatectomized patients. 44 30

Parenchymal cells from adult rat liver, cultured in perifused monolayers, increased the levels of urea-cycle enzymes between 15% and 60% in response to glucagon within 24 h. This stimulation was drastically enhanced by the simultaneous presence of dexamethasone, especially in the case of argininosuccinate synthetase and argininosuccinate lyase, which increased nearly threefold. Dexamethasone itself produced only negligible stimulation, but exerted a similar effect on the stimulatory action of glucagon, if it was exclusively present during 6 h prior to the glucagon treatment, suggesting a permissive action of this hormone. The effect of glucagon, particularly in the presence of dexamethasone, was mimicked by dibutyryl adenosine 3':5'-monophosphate, whereas epinephrine was ineffective. All stimulations induced by hormones or dibutyryl adenosine 3':5'-monophosphate were abolished by cycloheximide, suggesting the involvement of protein synthesis in the induction process. Using the usual culture technique with a discontinuous supply of medium no significant effect of glucagon and dexamethasone could be measured. This striking difference between both culture systems indicates that perifusion is the more adequate in vitro system for studies of the regulation of enzyme levels. Possible reasons for the failure of hormonal stimulation of urea-cycle enzymes in normal monolayer culture are discussed.
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PMID:Permissive effect of dexamethasone on glucagon induction of urea-cycle enzymes in perifused primary monolayer cultures of rat hepatocytes. 47 71

1. Heat output by suspensions of isolated rat hepatocytes was determined by using a modified batch-type microcalorimeter. 2. The ratio of O(2) uptake (determined polarographically) to heat output was used to assess the metabolic efficiency of isolated hepatocytes. 3. Cells from starved or fed rats incubated in either bicarbonate-buffered physiological saline containing gelatin, or bicarbonate-buffered physiological saline containing amino acids, serum albumin and glucose showed no significant difference with respect to the ratio of O(2) uptake to heat output. 4. For liver cells from 24h-starved rats, the addition of 10mm-dihydroxyacetone and 2.5mm-fructose significantly decreased the ratio of O(2) uptake to heat output from 1.94+/-0.05 in the controls to 1.52+/-0.04 and 1.54+/-0.01mumol/J respectively. 5. Glucagon (1mum), which slightly increased both O(2) uptake and heat output, did not significantly alter the ratio. 6. The addition of extracellular 10mm-NH(4)Cl and urease to provide an energetically wasteful cycle by ensuring hydrolysis of newly synthesized urea, lowered the ratio of O(2) uptake to heat output from 1.81+/-0.08 to 1.47+/-0.06mumol/J, indicating a reduced metabolic efficiency. 7. Metabolic efficiency in rats of different dietary regimen, age and genetically based obesity was also assessed. No differences in the ratio of O(2) uptake to heat output were found between liver cell suspensions prepared from rats maintained on colony diet and high-fat diet or sucrose-rich diet nor between animals ranging from 38 to 179 days of age. Comparison of the ratio of liver cell O(2) uptake to heat output between homozygote Zucker fa/fa obese rats and their lean littermates showed no significant difference. 8. It is concluded that the ratio of O(2) uptake to heat output for isolated hepatocytes is relatively constant unless perturbed by conditions that markedly enhance substrate cycling.
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PMID:The application of microcalorimetry to the assessment of metabolic efficiency in isolated rat hepatocytes. 48 37

Because the gastrointestinal hormones are known to dilate the splanchnic vasculature, their effects on transport of water and solutes during peritoneal dialysis were studied in an experimental model, the rabbit. In unanesthetized rabbits, dialysate volume was calculated by isotope dilution, and clearances were estimated by dialysate/plasma concentration ratio factored by minute volume. With isotonic dialysis solution, the mean increment in dialysate volume per minute of intraperitoneal dwell was 0.19 ml/kg/min, and mean clearances of creatinine and urea were 0.71 and 0.90 ml/kg/min, respectively. When administered intravenously, secretin significantly augmented osmotically induced water flux, but not when given intraperitoneally. Neither glucagon nor cholecystokinin affected dialysate volume. Intravenously, but not intraperitoneally, glucagon increased peritoneal clearances of creatinine and urea to more than 150% of control values. Neither cholecystokinin nor secretin augmented significantly peritoneal mass transport when given by either route. The data suggest that the site of acton is the endothelial surface of the membrane, that the mechanisms of augmenting transport involve increased permeability and/or surface area, and that agents which combine an increase in mass transport and capillary filtration coefficient may be clinically useful.
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PMID:Effects of gastrointestinal hormones on transport by peritoneal dialysis. 51 2

Hormonal and substrate profiles and urinary nitrogen and urea excretion were measured in 78 underweight patients admitted for surgical investigation, who were placed into either a normo- or a hyperketonemic group, depending upon their levels of acetoacetate and beta-hydroxybutyrate. The two groups were otherwise similar in terms of weight loss, arm muscle circumference, triceps skinfold thickness, and serum protein levels. Before surgery only one-quarter of them were hyperketonemic displaying mean glucose, insulin, and glucagon levels characteristic of starvation-adaption, and excreted significantly less urinary nitrogen than in normoketonemic group. Those patients who underwent surgery tended to retain their presurgery hormonal and substrate profile. The normoketonemic group excreted significantly greater amounts of urinary nitrogen, depleted body protein to a greater extent as evidenced by larger changes in arm muscle circumference and serum protein levels, and mortality was greater. Interference with insulin-glucagon balance by sepsis and disease is suggested as a possible explanation for the failure of three-quarters of the patients to become starvation-adapted. The implications of this finding on the parenteral feeding of undernourished patients are discussed.
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PMID:Ketosis and nitrogen excretion in undernourished surgical patients. 57 67

The methylation of the single methionine residue of glucagon is accomplished at a pH of 3.5 in 8 M urea with methyl iodide. The reaction product is a soluble sulfonium derivative, S-methylglucagon, which can be isolated in a highly purified form. This derivative is characterized by amino acid analysis and its effect on the adenylyl cyclase system of rat liver plasma membranes. S-Methylglucagon does stimulate the adenylyl cyclase system; however, its activity is approximately 500 times less than that observed with the native hormone. The solubility of this derivative is great enough to allow for further modifications of the molecule which can be followed at a later stage by demethylation. Demethylation of S-methylglucagon regenerates the original covalent structure and is accomplished by treatment with Cleland's reagents at a pH of 10.5. The regenerated hormone is indistinguishable from native glucagon by its amino acid composition and its ability to stimulate the adenylyl cyclase system. The entire methylation-demethylation reaction sequence has been carried out with yields that approach 75%. The technique is suitable for the isotopic enrichment of native glucagon and may well be applicable to selected other methionine-containing peptides.
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PMID:Methylation of glucagon, characterization of the sulfonium derivative, and regeneration of the native covalent structure. 58 56

Circadian variations in liver protein synthesis were were assessed in control rats fed a mixed 10% protein diet and in rats fed proteins as a separate meal either at 09:00 (SF 09) or at 21:00 (SF 21) and provided with a protein-free diet ad libitum. Protein synthesis was measured by incorporation of labelled leucine over a short period of time (15 min) at time-points regularly spaced over 24 h. In controls, the circadian variations observed were of moderate amplitude (from 2.75 mg/h per g at 09:00 to 5.77 mg/h per g at 06:00) correlated with increased protein and RNA contents of the liver. In separately fed animals ingestion of the protein meal triggered a 300% increase in protein synthesis within 1 h while the feeding pattern was unaltered. In the SF 09 group, high synthetic activity was not followed by an increase of hepatic protein content while hepatic urea concentrations were sharply increased and glucogenic amino acid pools were greatly depleted. It is suggested that the high influx of amino acids consecutive to the absorption of the dietary proteins is the key factor stimulating protein synthesis, while synchronisation with the energetic metabolism controls the degree of degradation. The possible involvement of variations in the insulin to glucagon ratio is discussed.
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PMID:Regulation of hepatic synthesis of proteins by the chronology of protein ingestion. 62 71


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