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)

DBcAMP or crystalline glucagon was utilized to elevate the intracellular cyclic AMP concentration in isolated rat hearts. Butyric acid, a metabolite of DBcAMP, was also investigated. Their effect on the intracellular pH (pHi) as determined by the distribution of [14C]DMO was investigated. Rat hearts, perfused with a recirculated modified Krebs-Henseleit solution maintained at 30 degrees C, were exposed to respiratory acidosis by bubbling the perfusate with 20% CO2. alpha- and beta-receptor antagonists were used to block the effects of endogenous catecholamines. Hypercapnia decreased the pHi from 7.09 to 6.82. A similar degree of hypercapnia decreased the pHi to only 6.95 in the presence of DBcAMP and to only 6.96 in the presence of glucagon. The effective buffer values (delta[HCO-3]i/deltapHi) were: control, 19; butyric acid, 16; DBcAMP, 139; glucagon, 148. These data suggest that cAMP mediates the effect of norepinephrine, which has been shown to diminish the change in pHi accompanying respiratory acidosis.
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PMID:The effect of dibutyryl cyclic AMP and glucagon on the myocardial cell pH1. 2 69

Prophylactic effect of 4-[(4-chlorobenzoyl)(4-methoxyphenyl)-amino]-butyric acid (clanobutine, Bykahepar) on restraint stress ulcer formation was studied in male albino rats. Number and size of ulcers were counted, pH value of gastric juice and plasma levels of corticoids, glucagon and blood sugar were measured. Rats treated with clanobutine had only the one-third of ulcers compared with the untreated animals. This effect was found to be dose-dependent. Clanobutine did not change plasma levels of corticoids, glucagon or blood sugar. Rise in pH value of gastric juice during stress exposition was found to be lower in clanobutine treated animals than in untreated controls. Blood flow in gastrointestinal tract was seen to be much better under the influence of clanobutine. The mechanism of action of clanobutine is discussed.
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PMID:[On the influence of clanobutine on the formation of restraint ulcer in rats (author's transl)]. 54 79

Basic studies on the secretion of glucagon and insulin by the ovine pancreatic autotransplant in the neck are described. Of the 17 transplants in the series none failed to secrete glucagon and only three failed to secrete insulin in detectable amounts. The longest surviving transplant actively secreted both hormones 3 years after transplantation and five other transplants were functional and the animals healthy after 16 months. Exocrine secretion disappears shortly after transplantation. Sodium butyrate and alanine each promoted the secretion of both hormones by the transplant. Glucagon failed to promote insulin secretion by the transplant, although it apparently stimulated the ovine in situ pancreas. The immediate (presumably direct) effect of insulin was to inhibit transplant glucagon secretion. Hypoglycaemia induced by peripheral insulin administration failed to stimulate glucagon secretion by the transplant, although it did promote glucagon secretion by the ovine in situ pancreas. Heparin did not markedly suppress basal transplant secretion of either glucagon or insulin. Phasic response patterns occurred with both hormones during long butyrate perfusions, although first-phase responsiveness was not a constant feature. In one trial, first-phase responses fell off with repeated short butyrate infusions. Glucagon and insulin secretory patterns in response to butyrate were remarkably alike, suggesting a common mechanism. Loss of specific functions by the ovine pancreas after transplantation is discussed.
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PMID:Studies with the autotransplanted ovine pancreas: glucagon and insulin secretion. 79 Dec 27

Six normal subjects received 10 g of alanine both orally and as a 60-min intravenous infusion. In both studies blood samples for hormones and substrates were obtained every thirty minutes for 2 1/2 hour. Significant increases in whole blood levels of threonine, serine, glutamine, proline, glycine, and alpha-amino-n-butyric acid were found, which were mainly due to increases of these amino acids in the plasma compartment. In contrast, whole blood levels of leucine, valine, and isoleucine declined, mainly due to increases in the cell compartment. Plasma glucagon levels increased in both studies while insulin levels rose significantly only during the oral study. Plasma free fatty acids and blood glycerol levels declined while lactate and pyruvate increased. Glucose concentration did not change during both tests. These data suggest that the administration of large quantities of alanine is capable of inducing significant alterations in levels of other amino acids and substrates as well as changing hormone levels.
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PMID:Alanine-induced amino acid interrelationships. 116 33

Current evidence suggests that a multipotential endodermal progenitor cell may give rise to all islet cell phenotypes. We characterized two hormone-producing rat islet (RIN) cell lines derived from a radiation-induced islet tumor by immunocytochemistry, Northern blot analysis, and radioimmunoassay of secreted hormone. Using antisera to glucagon, insulin, and somatostatin, we found that less than 15% of the cells in any of these three islet cell lines contained immunopositive cells. The number of cells staining for the hormone correlated with mRNA levels and immunoreactive secreted hormones. Sodium butyrate, a short-chain aliphatic fatty acid, slowed cell growth and increased dramatically the percentage of cells staining for glucagon and insulin. The increase in immunopositive cells was accompanied by an increase in glucagon and insulin mRNAs and secreted glucagon and insulin. These observations indicate that sodium butyrate increases glucagon and insulin gene expression by recruiting previously immunonegative cells to produce hormone. The relationship of DNA synthesis and hormone production was assessed by pulse-labeling RIN cells with [3H]thymidine, which was followed by autoradiography and immunocytochemistry. [3H]thymidine incorporation was observed in a lower percentage of immunopositive compared with immunonegative cells. Furthermore, sodium butyrate reduced the number of [3H]thymidine-labeled cells and increased the number of immunopositive cells. These observations suggest that sodium butyrate differentiates the islet cells and thereby increases the expression of the glucagon and insulin genes.
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PMID:Sodium butyrate increases glucagon and insulin gene expression by recruiting immunocytochemically negative cells to produce hormone. 284 9

The hepatic level of prostaglandins will reflect the balance between synthesis of prostaglandins and their rapid catabolism via beta-oxidation by hepatocytes. In the present study we examined the effect of physiological fuel substrates on the breakdown and action of prostaglandin E2 (PGE2) in isolated rat hepatocytes. Palmitic acid (0.32 mM), a long-chain fatty acid, inhibited the rate of PGE2 breakdown (10(-7) M) by approx. 80%. As the palmitic acid concentration was increased from 0 to 0.8 mM, the percentage of PGE2 remaining in the incubation 5 min following prostaglandin addition was raised from approx. 10% to over 98%. Octanoic acid (0.8 mM) also inhibited PGE2 catabolism, while butyric acid (0.8 mM) and pyruvic acid (2.5 mM) were without effect. The inhibition of glucagon-stimulated glycogenolysis by PGE2 was increased in the presence of 0.6 mM palmitic acid, consistent with decreased PGE2 catabolism. These studies demonstrate that changes within the range of free fatty acid concentrations seen physiologically in vivo may dramatically alter PGE2 catabolism and, therefore, the effect of PGE2 to modulate hormonal action in the liver.
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PMID:Modulation of prostaglandin E2 catabolism and action by fuel substrates in rat hepatocytes. 291 5

The state of differentiation of various neoplastic cell lines is inversely correlated with the rate of cellular growth. To delineate the changes in hormone gene expression associated with an induced decrease in the growth rate of rat insulinoma cells, we studied the effects of sodium butyrate on the expression of the genes encoding insulin, glucagon, and angiotensinogen. Sodium butyrate inhibited cellular proliferation and decreased levels of c-myc mRNA. Concomitantly, steady-state levels of mRNAs encoding insulin and glucagon increased by 10- and 8.5-fold, respectively, as a result of a specific increase in the transcription of both genes. Sodium butyrate also inhibited angiotensinogen gene expression, which was ectopic in the insulinoma cells. These observations suggest that sodium butyrate induces a pattern of events leading to the differentiation of the rat insulinoma cells.
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PMID:Transcriptional regulation of genes encoding insulin, glucagon, and angiotensinogen by sodium butyrate in a rat islet cell line. 355 Apr 24

Long-term ingestion of high fiber diets is associated with reduced glucose concentrations during fasting and improved glucose tolerance (KG) in humans. Our objective was to determine if the beneficial effects of fiber were attributable to increased production of short-chain fatty acid (SCFA) in the large intestine. Effects of SCFA on insulin sensitivity (SI), glucose effectiveness (SG), KG and baseline concentrations of glucose, insulin, glucagon and free fatty acids were examined in unfed 20-50 kg pigs (n = 6). Animals randomly received separate portal infusions (0.32 mL.min-1) of saline, acetic, propionic, and butyric acid solutions (0.01 mmol SCFA kg body weight-1.min-1) for 7-d periods. On d 7, somatostatin and tolbutamide modified frequently sampled intravenous glucose tolerance tests were performed. SI and SG were calculated using Bergman's Minimal-Model. KG was determined by regression of log glucose curve versus time. SI, SG and KG values did not differ among the treatments (P > 0.05). Baseline concentrations of glucose, insulin, glucagon and free fatty acids were unaffected by infusion treatment (P > 0.05). Our results suggest that SCFA delivery is not directly responsible for improvements in glucose metabolism observed with long-term ingestion of high fiber diets.
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PMID:Splanchnic infusions of short chain fatty acids do not change insulin sensitivity of pigs. 756 92

The chemical specificity and structural requirements of short-chain fatty acids (SCFAs) in stimulating pancreatic endocrine responses was investigated in conscious sheep. Normal SCFAs with one to eight carbons were injected intravenously at seven doses of 39-2,500 mumol/kg body wt. The isomers or derivatives of SCFAs were administered at 625 mumol/kg body wt. Analysis of dose-response curves showed that n-butyric acid (4 carbons in the molecule) was most effective for both insulin and glucagon secretion among the normal SCFAs tested. In addition, one carboxylic group was absolutely required, since hormone secretion was significantly reduced or abolished with compounds in which the carboxylic element was replaced by other groups and with dicarboxylic acids. The form of the hydrocarbon chain (branched, cyclic, or benzoic ring) also affected hormone secretory activity. Most of the compounds that replaced hydrogen in the hydrocarbon chain by other groups at various positions reduced or abolished the hormone secretory effect obtained by n-butyric acid. In conclusion, a monocarboxylic acid with several numbers of hydrocarbons was required for insulin or glucagon secretion. These results suggest that the pancreatic endocrine system can recognize the chemical structure of SCFAs in detail and induce hormone secretion in sheep.
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PMID:Chemical specificity of short-chain fatty acids in stimulating insulin and glucagon secretion in sheep. 807 2

The role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of exocrine and endocrine pancreas was investigated in conscious sheep. Intravenous infusions of PACAP-27 and PACAP-38 (1, 3, and 10 pmol/kg/min) for 10 min during phase II of the duodenal migrating myoelectric complex accelerated pancreatic protein and amylase outputs dose-dependently. The responses in enzyme secretion to both PACAPs at the highest doses were inhibited significantly by atropine infusion (14.4 nmol/kg/min). Vasoactive intestinal polypeptide (VIP) at 3 pmol/kg/min significantly accelerated protein but not amylase outputs, although the response to the highest dose was not significantly influenced by atropine. PACAP-27 and VIP increased pancreatic juice flow and bicarbonate output dose-dependently; however, the responses to the highest dose were not altered significantly by atropine. On the other hand, intravenous injection of PACAP-38 (100 pmol/kg) did not influence basal plasma concentration of insulin, glucagon, and glucose. Moreover, PACAP-38 (1-100 pmol/kg) altered neither pancreatic endocrine response to intravenous infusion of glucose (20 mumol/kg/min) not that to n-butyric acid (33 mumol/kg/min). These results suggest that PACAP contributes to the regulation of exocrine secretion of the ovine pancreas but not to endocrine secretion. PACAP appears to accelerate pancreatic enzyme secretion mostly via the cholinergic nerves.
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PMID:Effect of pituitary adenylate cyclase-activating polypeptide on exocrine and endocrine secretion in the ovine pancreas. 937 56


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