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)

Porcine vasoactive intestinal peptide stimulated adenosine 3':5'-monophosphate (cyclic AMP) production in rat intestinal epithelial cells. The stimulation was dependent on time and temperature and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Under optimal conditions (at 15 degrees C, with 0.2 mM 3-isobutyl-1-methylaxanthine, at a cell concentration up to 18 microgram DNA/ml), the cyclic AMP production produced by vasoactive intestinal peptide was constant for 10 min and stopped after 15 min incubation, at either low (1 nM) or high (30 nM) concentration of the peptide. This plateau effect was demonstrated not to be due to an inactivation of vasoactive intestinal peptide in the medium nor to an alteration of receptors for the peptide. Cyclic AMP production was sensitive to a concentration as low as 0.1 nM vasoactive intestinal peptide. Maximal stimulation of cyclic AMP levels by vasoactive intestinal peptide was observed with 30 nM vasoactive intestinal peptide and represented an 11-fold increased above basal. The dorse-response curve was monophasic with a Km of 2.3 x 10(-9) M. No cooperative effects were detected by Hill analysis. The positive non-linear relationship observed between stimulation of cyclic AMP production and occupancy of binding site was not time-dependent as indicated by experiments performed after 15, 45 and 120 min incubation. Maximal and half-maximal responses were obtained at about 70% and 7% occupation of binding sites, respectively. Chicken vasoactive intestinal peptide and porcine secretin were agonists of porcine vasoactive intestinal peptide with a 6-times and a 120-times lower potency, respectively. Among secretin analogs that were found to have low affinity for vasoactive intestinal peptide binding sites, [4-alanine, 5-valine]secretin, that resembles vasoactive intestinal peptide at the first seven amino acids at the N-terminal end, was a partial agonist of vasoactive peptide at the first seven amino acids at the N-terminal end, was a partial agonist of vasoactive intestinal peptide and others failed to stimulate cyclic AMP production. Glucagon (10microM), gastric inhibitory peptide (0.1 microM), substance, P, neurotensin, octapeptide of cholecystokinin, bovine pancreatic polypeptide, human gastrin I with leucine at residue 15, Leu-enkephalinand somatostatin (1 microM) did not alter cyclicAMP levels. Non-peptide mediators such as dopamine, serotonin, acetylcholine and histamine, tested at 10 microM, were also ineffective. Prostaglandins E2, E1 and isoproterenol, tested at 10 microM, induced an increase of cyclic AMP levels above basal but were 9.5, 13.7 and 17.5 times less efficient than vasoactive intestinal peptide, respectively. Thus vasoactive intestinal peptide is a unique stimulus of cyclic AMP production in rat intestinal epithelial cells.
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PMID:Interaction of vasoactive intestinal peptide with isolated intestinal epithelial cells from rat. 2. Characterization and structural requirements of the stimulatory effect of vasoactive intestinal peptide on production of adenosine 3':5'-monophosphate. 8 68

Sepsis is a major catabolic insult resulting in modifications in carbohydrate and fat energy metabolism, and leading to increased muscle breakdown and nitrogen loss. Insulin resistance, which develops in sepsis, decreases glucose utilization, but plasma insulin levels are sufficiently elevated to prevent lipolysis, resulting in a further energy deficit. The availability of fuels in sepsis is therefore limited, and the body resorts to muscle breakdown, gluconeogenesis, and amino acid oxidation for energy supply. Previous work has not defined, however, the exact alterations in amino acid metabolism. Therefore, the following studies were undertaken. Blood samples were drawn from fifteen patients in whom the diagnosis of sepsis was clinically established; the samples were analyzed for amino acid, beta-hydroxyphenylethanolamines, glucose, insulin and glucagon concentrations. The plasma amino acid pattern observed was characterized by an increase in total amino acid content, due mainly to high levels of the aromatic amino acids (phenylalanine and tyrosine) and the sulfur-containing amino acids (taurine, cystine and methionine). Alanine, aspartic acid, glutamic acid and proline were also elevated, but to a lesser degree. The branched chain amino acids (valine, leucine and isoleucine) were within normal limits, as were glycine, serine, threonine, lysine, histidine and tryptophan. Those patients who did not survive sepsis had higher levels of aromatic and sulfur-containing amino acids as compared to those patients surviving sepsis. On the other hand, those patients surviving sepsis had higher levels of alanine and the branched chain amino acids. In a second group of five patients with overwhelming sepsis accompanied by a state of metabolic encephalopathy, a parenteral nutrition solution consisting of 23% dextrose, and an amino acid formulation enriched with branched chain amino acids was administered. In these five patients, normalization of the plasma amino acid pattern and reversal of encephalopathy was observed. The following sequence of events may be postulated: The septic patient develops insulin resistance in the peripheral tissues, primarily muscle, while the adipose tissue is much less affected. The insulin resistance and the inability to utilize fat leads to increased muscle proteolysis. Muscle breakdown results in release into the blood of enormous amounts of various amino acids; the muscle itself is able to oxidize the branched chain amino acids, supplying the muscles' own energy requirements and alanine for gluconeogenesis. The extensive muscle proteolysis coupled with relative hepatic insufficiency occurring early in sepsis results in the appearance in the plasma of high levels of most of the amino acids present in muscle, particularly the aromatic and the sulfur-containing amino acids. The outcome of patients with sepsis might be positively affected by combined therapy with glucose, insulin and branched chain amino acids.
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PMID:Amino acid derangements in patients with sepsis: treatment with branched chain amino acid rich infusions. 9 98

Two groups (each of 6 moderately ill, protein-depleted patients) were infused daily for 7 days. Mean 7 day nitrogen (N) balances with infusions of 0.83 and 1.83 g of a defined amino acid mixture (containing further nutrients but no other source of energy)/kg ideal body wt/day were -3.66 and +1.54 g/day, respectively (P less than 0.025) when adjusted for changes in body urea and estimated miscellaneous N losses. Concentrations of plasma free fatty acids, immunoreactive insulin and glucagon, and of blood glucose, pyruvate, lactate and glycerol were indistinguishable on corresponding treatment days in the 2 groups but blood ketone bodies were lower in the 1.83 g/kg group. Blood amino acid concentrations of alanine, valine, leucine, and isoleucine were similar, whereas those of phenylalanine, histidine, serine, and arginine were higher, and glutamine lower, in the 1.83 g/kg group. The data confirm that not only can body protein mass be maintained, but a net positive N retention achieved, in such patients, through provision of exogenous amino acids and concurrent mobilization of endogenous energy stores. Of note is that this fat mobilization can occur without plasma free fatty acids and/or significant blood ketone body elevations. An infusion of 2, rather than 1 g/kg/day seems suitable in the situation examined.
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PMID:Intravenous protein-sparing therapy in patients with gastrointestinal disease. 11 60

Alloxan diabetic rats maintained on protamine zinc insulin for two weeks were used for these studies. Hepatocytes were isolated from these rats at various time intervals after withdrawal of insulin (0, 48, 72 and 96 hr). Gluconeogenesis with various concentrations of lactate and fructose was studied. Both lactate and fructose stimulated gluconeogenesis and showed progressive increases in glucose production up to 72 hr after the insulin withdrawal. Glucose production decreased at 96 hr. Protein synthesis in isolated hepatocytes from diabetic liver cells, as measured by the incorporation of radioactive isoleucine, valine and phenylalanine into protein, showed a decrease (5- to 6-fold) with time after insulin withdrawal. Glucagon (10(-6)M) alone increased cyclic AMP levels 10-fold in liver cells, in isolated cells from rats maintained on insulin (0 hr) or from rats withdrawn from insulin for 48 hr. The ability of glucagon to elevate cyclic AMP levels in isolated diabetic liver cells decreases 72 hr following insulin withdrawal.
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PMID:Studies on gluconeogenesis, protein synthesis and cyclic AMP levels in isolated hepatocytes from alloxan diabetic rats. 17 99

In 10 fasting dogs receiving 10(9) viable E. coli bacteria per kilogram intravenously, mean systolic blood pressure decreased from 120.6 +/- 15.1 to 82.2 +/- 12.8 mm Hg. The association of hypoglycemia and increased arterial alanine and glycine with elevated plasma glucagon implied impaired gluconeogenesis. A rapid elevation of blood urea concentration, indicating increased ureagenesis, a fall of blood glucose, and an increase of net urea synthesis relative to that of glucose suggested that an increased proportion of the carbon residues derived from glucogenic amino acids is catabolized via pathways other than gluconeogenesis. In the bacteremic dogs the absolute net release from the leg of valine, isoleucine, and leucine and their net release relative to the net rate of proteolysis were decreased, suggesting increased oxidation of these amino acids in skeletal muscle. An increased net release of alanine relative to the net rate of protein catabolism in muscle was in agreement with this contention.
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PMID:Amino acid metabolism in dogs with E. coli bacteremic shock. 36 15

In ten patients with a femoral shaft fracture, arterial plasma amino acids and glucagon, blood glucose, and serum insulin were measured after an overnight fast on the third, fifth, and seventh days following injury. Ten normal subjects were controls. On all days, concentrations of the key glucogenic amino acid, alanine, were the same in both groups, but levels of another glucogenic amino acid, glycine, were significantly less in the fracture patients. Other amino acid changes following injury were maximal at 7 days, with significant elevations of phenylalanine, methionine, tyrosine, ornithine, lysine, arginine, valine, isoleucine, and leucine. Increased levels of insulin, glucose, valine, isoleucine, and leucine on the fifth and seventh days after injury implied insulin resistance. Plasma glucagon was elevated on the third (p less than 0.05) and seventh (p less than 0.01) days after injury, but the concentrations measured are insufficient to explain the impaired carbohydrate tolerance following a fracture.
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PMID:Arterial plasma amino acids during the first week following femoral shaft fracture. 43 79

An oral phenylalanine load provokes a significant drop in serum tyrosine levels in children with phenylketonuria [8]. The aim of the present investigation was to examine the response of insulin and glucagon to oral phenylalanine loading as these hormones are known to have a hypoaminoacidaemic effect. Six adult normal weight and healthy men were loaded orally with 0.6 mmol L-phenylalanine per kg body weight after an overnight fast. Serum phenylalanine increased within 10 min after the load and reached a maximum concentration at 30 min. Serum tyrosine increased within 10 min after the load and reached a maximum concentration at 2 h. Plasma glucagon and insulin increased during the first 10 min after the load and reached a peak twice the fasting levels at 30 min after the load. The molar insulin/glucagon ratio remained unchanged during the first 20 min after the load but then declined by 50% at 2 h. Associated with this decline plasma amino acid concentration (except phenylalanine and tyrosine) declined by approximately 15%. The decline was most marked for isoleucine, leucine, methionine and valine. As the hypoaminoacidaemic effect of insulin and glucagon is known to be most marked for these four amino acids plus phenylalanine and tyrosine, the response of insulin and glucagon to a phenylalanine load may influence not only the fate of phenylalanine given but also the blood tyrosine level.
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PMID:Effects of oral phenylalanine load on plasma glucagon, insulin, amino acid and glucose concentrations in man. 66 49

To evaluate the effect of insulin-saline-bicarbonate therapy on amino acid metabolism in diabetic ketoacidosis, arterial and venous blood samples as well as cerebrospinal fluid (CSF) were obtained from six patients before and after initiation of corrective therapy. Levels of CSF glutamine were decreased while alanine alpha-amino-n-butyrate, valine, isoleucine and leucine were increased significantly compared to a control group composed of six normal, postabsorptive adults free of any neurologic disease. Following therapy, CSF levels of alanine, alpha-amino-n-butyrate, valine, isoleucine, and leucine declined while glutamine levels did not change. Admission arterial plasma levels of the glycogenic amino acids were lower than normal while the branched-chain amino acids were elevated. Plasma alanine and glutamine arterio-venous (A-V) differences across forearm tissue were larger. After four hours of corrective therapy, arterial plasma levels of most of the amino acids had declined sharply and A-V differences for glutamine and alanine were markedly reduced (p smaller than.025 and p smaller than.01, paired t, respectively). Coincident with the decrease in A-V amino acid differences, plasma glucagon and free fatty acid levels declined significantly. These data suggest that the effect exerted by insulin-saline-bicarbonate therapy on amino acid metabolism is manifested by diminished A-V plasma alanine and glutamine differences across forearm tissue. Thus, the role played by the splanchnic bed both before and following corrective measures may be secondary to substrate availability.
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PMID:Plasma and cerebrosponal fluid amino acid levels in diabetic ketoacidosis before and after corrective therapy. 80 76

The alpha-ketoanalogues of the branched-chain amino acids were administered to fasting subjects to determine whether or not they promoted nitrogen sparing. Two fasting studies were carried out in each subject. During the first week of one of the two fasts 4.7 g of a mixture of the alpha-ketoanalogues of valine, leucine, and isoleucine were infused daily. No infusions were administered during the other fast, which served as a control. Urinary urea and calculated total urinary nitrogen were significantly lower during both the week of infusions and the ensuing week of fasting after the infusions were discontinued. Immediately after ketoacid infusions, plasma branched-chain amino acids, including allosioleucine, rose, while alanine and several other amino acids (but not glutamine) fell. There were no differences between the two fasts with respect to ketone bodies, free fatty acids, glucose, insulin, or glucagon concentrations. We conclude that branched-chain ketoacids spare nitrogen early in fasting and that this effect persists after they are metabolized.
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PMID:Nitrogen sparing induced early in starvation by infusion of branched-chain ketoacids. 83 56

The effect of glucagon on hepatic protein systhesis and proteolysis has been investigated. The intraperitoneal administration of 200 mug of glucagon produced an increase of the polypeptide chains completion time which was maximal 5 min after its administration and approached control values at 20 min. The increase of the polypeptides chains completion time observed at 5 min after the hormone administration represents a 38% inhibition of the hepatic protein synthetic rate. When glucagon was continuously supplied by intravascular infusion, maximal inhibition was attained throughout the experiment. This inhibition of protein synthesis brought about by glucagon was accompanied by an increase in the polyribosomal state of aggregation, indicating that the hormone acts mainly if not exclusively, on the elongation or termination step, or both. The administration of glucagon produced also a progressive increase in the hepatic valine concentration. This increase could not be accounted for the the decrease in plasma valine levels, suggesting that the rise in haptic valine concentration is an expression of hepatic proteolysis rather than the result of an accelerated transport of amino acids across the hepatocyte plasma membrane. The different time sequence in the glucagon-induced effects of protein synthesis and proteolysis suggests that both effects are independent and probably mediated by different mechanisms.
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PMID:Role of glucagon on the control of hepatic protein synthesis and degradation in the rat in vivo. 100 12


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