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)

We measured several growth stimulating variables in growth retarded (small-for-gestational-age [SGA]) rat fetuses on days 18, 19, 20, and 21 of their 21.5-day gestation. Bilateral maternal uterine artery ligation on day 18 was used to retard fetal growth, and fetuses of sham and nonoperated (normal) mothers served as controls. SGA fetuses had the lowest body and placental weights, while sham fetuses had intermediate weights from days 19 to 21. Similarly, SGA fetuses had the most profound alterations in arteriovenous PO2, PCO2, and pH, while sham fetuses had significant but less severe alterations. Fetal plasma concentrations and fetal/maternal ratios of glucose were significantly diminished in SGA fetuses on days 18 and 19; sham fetuses had intermediate values on day 19. Plasma concentrations and fetal/maternal ratios of leucine, isoleucine, and valine, but not the other amino acids, were significantly diminished in SGA fetuses on days 18, 19, and 20. Plasma insulin concentrations were significantly diminished in SGA fetuses on days 19 and 20, and hepatic concentrations of glycogen were significantly diminished on all days. Despite significantly elevated plasma glucagon concentrations in SGA fetuses, hepatic cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity was not elevated. These data indicate that bilateral uterine artery ligation retards fetal growth in the rat by altering gas exchange and limiting fuel availability. The limited insulin in SGA fetuses might further have retarded growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered gas exchange, limited glucose and branched chain amino acids, and hypoinsulinism retard fetal growth in the rat. 353 62

Our previous studies on carbohydrate structures of purified porcine spleen cathepsin B indicated that there are two cathepsin B isozymes, each containing a different carbohydrate (Takahashi, T., Schmidt, P.G., and Tang, J. (1984) J. Biol. Chem. 259, 6059-6062). We have now isolated these two enzymes and carried out a comparative study on their structures and enzymic properties. The major isozyme (CB-I) is a two-chain enzyme (Mr = 28,000) with a light chain (Mr = 5,000) and a heavy chain (Mr = 23,000), whereas the minor enzyme (CB-II) is a single chain enzyme (Mr = 27,000). The NH2-terminal amino acid residues of CB-I were leucine and valine for the light and heavy chain, respectively. However, the NH2-terminal residue of CB-II was not available for automated Edman degradation. In addition, peptide mapping experiments indicated a difference in the primary structure of these two proteins. Despite such structural differences, they are similar in many enzymic properties. CB-I was more catalytically efficient than CB-II toward synthetic substrates, except for the substrate benzoyl-L-arginine beta-naphthylamide for which the relative catalytic efficiency is reversed. Both isozymes degraded glucagon by a dipeptidyl carboxypeptidase activity. Under the same conditions, CB-I was 4-5 times more efficient than CB-II. The results indicate that the cathepsin B isozymes are two separate gene products, but they are similar in enzymic properties.
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PMID:Comparative studies of two cathepsin B isozymes from porcine spleen. Isolation, polypeptide chain arrangements, and enzyme specificity. 372 2

The effects of chronic (72 h) glucagon treatment on active nutrient uptake by the rat jejunum have been determined using in-vitro electrophysiological and autoradiographic methods together with an in-vivo technique which measures absorption across a cannulated segment of upper jejunum. Glucagon caused a marked increase in the potential difference across the brush border membrane from a mean value of -47.6 mV under control conditions to -54.2 mV following treatment with the hormone (P less than 0.025). A similar hyperpolarization was also noted after 24 h glucagon administration. The magnitude of the depolarization induced by the addition of D-galactose (4 mmol/l) to the mucosal fluid was increased from 6.0 to 14.3 mV following 72 h glucagon treatment (P less than 0.05). Phloridzin (0.1 mmol/l) abolished the galactose-induced depolarization in both control and treated animals. Glucagon induced significant increases of 49.9 and 61.0% respectively for glucose and galactose absorption measured under in-vivo conditions. Autoradiographic studies revealed that following glucagon treatment, L-valine uptake occurred earlier during enterocyte migration along the villus. This resulted in an enhanced accumulation of the amino acid at the villus tip. We conclude that glucagon increases nutrient transport across the small intestine. The raised electrical gradient for Na+- coupled nutrient entry into the enterocyte is likely to be a major factor in the transport response.
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PMID:Hyperglucagonaemia: effects on active nutrient uptake by the rat jejunum. 378 84

The effect of 20 L-amino acids upon pancreatic glucagon secretion has been studied in conscious dogs. Each amino acid was administered intravenously over a 15 min period in a dose of 1 mmole/kg of body weight to a group of four or five dogs. Pancreatic glucagon and insulin were measured by radioimmunoassay. 17 of the 20 amino acids caused a substantial increase in plasma glucagon. Asparagine had the most glucagon-stimulating activity (GSA), followed by glycine, phenylalanine, serine, aspartate, cysteine, tryptophan, alanine, glutamate, threonine, glutamine, arginine, ornithine, proline, methionine, lysine, and histidine. Only valine, leucine, and isoleucine failed to stimulate glucagon secretion, and isoleucine may have reduced it. No relationship between glucagon-stimulating activity and insulin-stimulating activity was observed. The amino acids which enter the gluconeogenic pathway as pyruvate and, which are believed to provide most of the amino acid-derived glucose, had a significantly greater GSA than the amino acids which enter as succinyl CoA or as alpha-ketoglutarate. However, pyruvate itself did not stimulate glucagon secretion. The R-chain structure of the amino acid did not appear to be related to its GSA, except that the aliphatic branched chain amino acids, valine, leucine, and isoleucine, were devoid of GSA.
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PMID:Glucagon-stimulating activity of 20 amino acids in dogs. 463 19

Albumin synthesis was measured in the isolated perfused rat liver by using the livers of both well-fed and starved rats. Starvation markedly decreased albumin synthesis. The livers from starved rats were unable to increase synthesis rates after the addition to the perfusates of single amino acids or the addition of both glucagon and tryptophan. Arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine, added together to ten times their normal peripheral blood concentrations, restored synthesis rates to normal. The plasma aminogram (i.e. the relative concentrations, of amino acids) was altered by depriving rats of protein for 48h. The use of blood from the deprived rats as perfusate, instead of normal blood, decreased albumin synthesis rates significantly by livers obtained from well-fed rats. The addition of single amino acids, including the non-metabolizable amino acid, alpha-aminoisobutyric acid, to the above mixture increased albumin synthesis rates to normal values. It is concluded that amino acids play an important role in the control of albumin synthesis and that more than one mechanism is probably involved.
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PMID:The effects of amino acids on albumin synthesis by the isolated perfused rat liver. 465 17

Splanchnic and leg exchange of glucose, lactate, pyruvate, and individual plasma amino acids was studied in diabetics 24 hr after withdrawal of insulin and in healthy controls. Measurements were made in the basal postabsorptive state and during the administration of glucose at a rate of 2 mg/kg per min for 45 min. In the basal state, net splanchnic glucose production did not differ significantly between diabetics and controls. However, splanchnic uptake of alanine and other glycogenic amino acids was 1(1/2)-2 times greater in the diabetics, while lactate and pyruvate uptake was increased by 65-115%. Splanchnic uptake of these glucose precursors could account for 32% of hepatic glucose output in the diabetics, as compared to 20% in the controls. This increase in precursor uptake was a consequence of a two- to threefold increment in fractional extraction of these substrates inasmuch as arterial levels of alanine, glycine, and threonine were reduced in the diabetics, while the levels of the remaining substrates were similar in the two groups. Peripheral output of alanine and other glycogenic amino acids as reflected in arterio-femoral venous differences was similar in both groups. An elevation in arterial valine, leucine, and isoleucine was observed in the diabetics, but could not be accounted for on the basis of alterations in splanchnic or peripheral exchange of these amino acids. Administration of glucose (2 mg/kg per min) for 45 min resulted in an 80% reduction in splanchnic glucose output in controls, but failed to inhibit hepatic glucose release in the diabetics despite a twofold greater increment in arterial glucose levels. In both groups no consistent changes in arterial glucagon were observed during the infusion. It is concluded that in nonketotic diabetics (a) total splanchnic output of glucose is comparable to controls, but the relative contribution of gluconeogenesis may be increased by more than 50%; (b) accelerated splanchnic uptake of glucose precursors is a consequence of increased hepatic extraction of available substrates rather than a result of augmented substrate supply; and (c) the failure of glucose infusion to inhibit hepatic glucose output suggests that the exquisite sensitivity of the liver to the infusion of glucose in normal man is a consequence of glucose-induced insulin secretion.
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PMID:Splanchnic and peripheral glucose and amino acid metabolism in diabetes mellitus. 503 28

In order to investigate disturbances in glycoregulation and plasma amino acids and their possible relationship in alcoholic liver diseases, plasma concentrations of insulin, C-peptide, glucagon and branched-chain (valine, leucine, isoleucine) as well as aromatic (phenylalanine, tyrosine) amino acids were measured during an arginine test (i.v infusion of arginine chloride 0.5 g/kg over 30 min) in 21 alcoholic patients: 11 with cirrhosis (group C) and 10 with steatosis (group S). Insulin responses to arginine was reduced in both groups, whereas glucagon response was increased in group C and reduced in group S. Plasma concentrations of branched-chain amino acids were reduced in both groups, irrespective of the degree of hyperinsulinism. Plasma concentrations of aromatic amino acids were increased only in cirrhotic patients; the increase was independent of the degree of hyperglucagonism and of the plasma insulin/glucagon molar ratio. These results suggest that disturbances of glycoregulation in plasma amino acids imbalance do not play a major role in alcoholic cirrhosis and steatosis.
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PMID:[Disturbances in glycoregulation and plasma amino acids in alcoholic hepatopathies. Study using the arginine test]. 623 16

Insulin and glucagon stimulate amino acid transport in isolated rat hepatocytes. Amiloride, a specific Na+-influx inhibitor, completely inhibited the hormonal (glucagon or insulin) stimulation of alpha-aminoisobutyric acid influx by preventing the emergence of a high-affinity transport component. The drug also inhibited [14C]valine incorporation into hepatocyte protein. The half-maximal concentration of amiloride for inhibition of protein synthesis was similar to that required for inhibition of hormone-stimulated amino acid transport (approx. 0.1 mM). In primary cultured rat hepatocytes, amiloride markedly depressed the stimulation of alpha-aminoisobutyric acid transport by glucagon, or a mixture of glucagon, insulin and epidermal growth factor. These results suggest that amiloride inhibits the hormonal stimulation of hepatocyte amino acid transport by preventing the synthesis of high-affinity transport proteins. They also suggest that the hormonal stimulation of hepatocyte amino acid transport is dependent, at least partly, on Na+ influx.
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PMID:The effect of amiloride on hormonal regulation of amino acid transport in isolated and cultured adult rat hepatocytes. 626 11

V1 vasopressin, angiotensin, alpha-adrenergic, and glucagon receptors in liver were studied on membrane fractions prepared from two groups of jerboas ( Jaculus orientalis) given dry or water-enriched diets for periods of 4 to 7 weeks, and from rats acutely treated with pharmacological amounts of arginine-vasopressin (AVP) or (1-deamino-8-D-arginine)-vasopressin (dDAVP). Tritiated (8-lysine)-vasopressin ([3H]vasopressin), tritiated (1-asparagine-5-valine)-angiotensin II ([3H]angiotensin II), tritiated dihydroergocryptine ([3H] DHEC ), and iodinated glucagon ([125I]-glucagon) were used as specific labeled ligands of these receptors. The V1 vasopressin, angiotensin, alpha-adrenergic, and glucagon receptors detected in both groups of jerboas were identical to receptors found in rat liver plasma membranes in regard to the apparent dissociation constants for their respective labeled ligands. Furthermore, vasopressin receptors in jerboa liver membranes discriminated as efficiently as rat liver receptors between the natural neurohypophyseal peptides arginine-vasopressin and lysine-vasopressin on the one hand and the structural analogs (1-deamino-8-D-arginine)-vasopressin and (4-valine-8-D-arginine)-vasopressin on the other. The reduction of antidiuretic hormone (ADH) secretion in jerboas fed a water-enriched diet compared to those on a dry diet (75 +/- 25 pM versus 372 +/- 86 pM) was accompanied by an increase in the number of liver vasopressin receptors (2.79 +/- 0.53 versus 1.25 +/- 0.14 pmol [3H]vasopressin bound/mg protein). The modifications observed were specific for vasopressin receptors, as judged by the maximal binding capacities of [3H]angiotensin II, [3H] DHEC , and [125I]-glucagon, which remained unchanged in jerboas whatever the levels of endogenous circulating ADH. Similarly, administration of pharmacological doses of AVP by iv infusion to rats induced, 2 hr later, a loss of about 50% of V1 liver vasopressin receptors, while the numbers and apparent dissociation constants of angiotensin, alpha-adrenergic, and glucagon liver receptors remained unchanged, and V2 kidney vasopressin receptors were almost desensitized. For V1 liver and V2 kidney vasopressin receptors, the desensitization process was strikingly dependent on the antidiuretic/glycogenolytic activity ratio of the peptide used. Thus, im injection to rats of dDAVP (an analog possessing a very high antidiuretic/glycogenolytic activity ratio) induced, 1 hr later, a total loss of V2 kidney receptors without modification of the number and apparent dissociation constant of V1 liver receptors.
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PMID:Plasma antidiuretic hormone levels and liver vasopressin receptors in the jerboa, Jaculus orientalis, and rat. 632 98

Plasma amino acids, glucagon, and insulin concentrations were determined once a week in dogs that developed acute hepatic necrosis and chronic hepatic insufficiency after treatment with dimethylnitrosamine. During the acute phase, plasma concentrations of most amino acids increased, with the changes usually correlating with increased glucagon values. Insulin correlated with changes in 10 of 21 amino acids, but the latter were not the most abundant nor the branched-chain amino acids. During the chronic phase, plasma phenylalanine tyrosine, and methionine concentrations remained increased throughout the study. Plasma values of these amino acids did not correlate with plasma concentrations of either glucagon or insulin. The values of the most abundant amino acids were less than base-line levels during the chronic phase, and 9 of 10 of these correlated positively with glucagon concentrations, but not insulin. Only proline correlated positively with insulin. Isoleucine and valine showed a negative correlation with insulin. The low concentrations of the nonaromatic amino acids increased during the time from the early to late chronic phase, during which time plasma glucagon increased and insulin remained unchanged. This study shows that a significant positive correlation existed between glucagon and the most abundant plasma amino acids during the chronic phase of hepatic insufficiency, at which time most plasma amino acid concentrations were returning toward base line. Increased glucagon values did not correlate with any evidence for deterioration of hepatic function.
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PMID:Plasma amino acid, glucagon, and insulin concentrations in dogs with nitrosamine-induced hepatic disease. 635 78


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