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 glucagon was studied on the isolated gastric fundus from immature rats in comparison with histamine. Glucagon (10(-7) -3 X 10(-6) M) caused a concentration-dependent increase in acid output, being approximately 25 fold more potent than histamine (ED50 values were 6.38 X 10(-7) M and 2.42 X 10(-5) M for glucagon and histamine, respectively). These compounds, however, did not differ in regard to the maximum response. The stimulatory effect of glucagon was not enhanced by pretreatment with 3 X 10(-8) M forskolin or 10(-7) M ICI 63197, a phosphodiesterase (PD) inhibitor. Conversely, both forskolin and ICI 63197 shifted to the left the concentration-response curve to histamine. The increase in acid secretion by glucagon was reduced by PGE1 (10(-5) M) and PGE2 (10(-5) M) but only PGE2 inhibited the response to histamine. From these data it can be concluded that glucagon stimulated acid production in the stomach from immature rats, and this effect does not seem to involve the same adenylate cyclase activated by histamine.
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PMID:Effect of glucagon on gastric acid secretion by the isolated fundus from immature rats. 283 65

The effect of E-series prostaglandins (PGE) on hormone-stimulated glycogenolysis was studied in isolated rat hepatocytes. As previously reported, the physiologically active analogue 16,16-dimethyl-PGE2 inhibited glucagon-stimulated glycogenolysis. This effect could be reproduced by repetitive addition of PGE2 to compensate for PGE2 catabolism. In contrast, glycogenolysis stimulated by N6,O2'-dibutyryladenosine-3',5'-cyclic monophosphate (dibutyryl-cAMP) was unaffected by either PGE2 or 16,16-dimethyl-PGE2 (rate of glycogenolysis with 0.34 microM dibutyryl-cAMP plus 1.7 microM 16,16-dimethyl-PGE2 = 99 +/- 6% of rate with 0.34 microM dibutyryl-cAMP alone; mean +/- SEM, N = 5). Similarly, glycogenolysis stimulated by 8-bromoadenosine-3',5'-cyclic monophosphate was not inhibited by PGE2 or 16,16-dimethyl-PGE2. Epinephrine-stimulated glycogenolysis was inhibited by 16,16-dimethyl-PGE2 in a dose-dependent manner. PGE inhibited the cAMP-independent stimulation of glycogenolysis resulting from phenylephrine or angiotensin II exposure (rate of glycogenolysis with 8 microM phenylephrine + 1.7 microM 16,16-dimethyl-PGE2 = 65 +/- 10% of rate with 8 microM phenylephrine alone, N = 4, P less than 0.05; 4.9 microM angiotensin II + 1.7 microM 16,16-dimethyl-PGE2 = 75 +/- 7% of rate with 4.9 microM angiotensin II alone, N = 4, P less than 0.05). Glycogenolysis stimulated by the calcium ionophore A23187 was also inhibited by PGE (rate of glycogenolysis with 0.55 micrograms/ml A23187 + 1.7 microM 16,16-dimethyl-PGE2 = 83 +/- 5% of rate with 0.55 micrograms/ml A23187 alone, N = 7, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of E-series prostaglandins on cyclic AMP-dependent and -independent hormone-stimulated glycogenolysis in hepatocytes. 298 82

Several studies have found high cAMP content in hepatomas in vivo, while hepatoma cells in vitro have very low levels. To explore this discrepancy and the regulation of cAMP in hepatomas, we have examined the cell line MH1C1 from Morris hepatoma 7795. These cells in culture contained low intracellular cAMP concentrations (approximately 0.5 pmol/mg protein at confluency), and were unresponsive to glucagon and prostaglandins (PG) E1 and E2. In contrast, solid hepatomas in rats developed from inoculates of MH1C1 had a 40-fold higher basal cAMP concentration and were stimulated by PGE1 and PGE2. Fibroblasts cultured from these tumours also contained high cAMP levels and responded strongly to PGE1. This may suggest that the difference in cAMP regulation between hepatomas in vivo and hepatoma cells in vitro results from the presence of other cells in the solid tumour rather than from selection of low-cAMP cells during the cloning procedure. Low-Km and intermediate-Km cAMP phosphodiesterase activity was high in MH1C1, compared to normal hepatocytes. This might contribute to the low cAMP level. The ability of MH1C1 to form cAMP was not defective, as the level could be increased more than 200-fold by beta-adrenergic activation in the presence of the phosphodiesterase inhibitor methylisobutylxanthine.
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PMID:The regulation of cyclic AMP levels in cultured MH1C1 rat hepatoma cells and in solid tumours derived from MH1C1 cell inoculates. 303 96

A bovine milk diet (BM) resulted in remarkable changes in histamine H2 receptor activity (sensitization) and PGE2 receptor activity (desensitization) in gastric glands isolated from adult rats. In contrast, the receptor-cAMP systems sensitive to glucagon(s) and secretin in parietal cells and muco-peptic cells were unaffected. In the two experimental groups, cimetidine produced a parallel displacement of the histamine dose-response curve suggesting competitive inhibition between this classical H2 receptor antagonist and histamine. The BM diet reduced the histidine decarboxylase activity in rat gastric mucosa; the histamine content was not significantly different in control and BM-fed rats. There was no alteration of the circadian rhythm of the parietal cell (ultrastructural changes: microvilli, tubulo-vesicles) determined at intervals of 6 hours in milk-fed rats. Prostaglandins and other components in milk (EGF, somatostatin, etc.) might therefore protect gastric mucosa by a differential control of PGE2 and histamine H2 receptor activity, either directly (PGE2 and EGF in milk) or indirectly (inhibition of endogeneous histamine synthesis/release and stimulation of prostaglandin synthesis/release).
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PMID:Effect of a milk diet on rat gastric mucosa: receptor activity, histamine metabolism and ultrastructural analyses. 303 66

Prostaglandin E2 (PGE2) can modulate the actions of a number of hormones in liver. PGE2 is rapidly metabolized in liver tissue, and thus alterations in the rate of PGE2 catabolism might exert a short-term influence on the concentration of PGE2 in liver. The present study examined the effects of inhibitors of oxidative metabolism on PGE2 catabolism and action in isolated rat hepatocytes. [3H]-PGE2 was metabolized to three major products by the hepatocyte system as assessed by reverse-phase high performance liquid chromatography. Metyrapone (5 mM), aminopyrine (5 mM), SKF-525A (20 microM) and alpha-naphthoflavone (20 microM) each inhibited the breakdown of [3H]-PGE2. The inhibition of oxidative metabolism by these compounds was not limited to action at cytochrome P-450, and metyrapone, aminopyrine and SKF-525A each was shown to inhibit [1-14C]-palmitate beta-oxidation in the hepatocyte system. To determine the contribution of beta-oxidation to the rapid catabolism of [3H]-PGE2, studies were performed using [1-14C]-PGE2 as substrate. Two major product peaks seen with [3H]-PGE2 as substrate lacked radioactivity when [1-14C]-PGE2 was the substrate, and thus these two products did not contain the 1-position carbon, consistent with their identity as beta-oxidation products. Furthermore, [1-14C]-PGE2 also yielded 14CO2 and a [14C]-PGE2 metabolite not seen with [3H]-PGE2. It was calculated that 60% of the rapid PGE2 inactivation in the hepatocyte system occurred via beta-oxidation. An additional, non-beta-oxidation, metyrapone-sensitive, pathway accounted for 26% of PGE2 disappearance. The effect of PGE2 to inhibit glucagon-stimulated glycogenolysis was potentiated when metyrapone was included in the incubation, consistent with increased survival of intact PGE2. In summary, PGE2 was rapidly inactivated by intact hepatocytes via oxidative metabolism, primarily beta-oxidation. Inhibition of prostaglandin catabolism can have short-term effects on PGE2 concentrations and result in potentiation of PGE2 effects on hepatic glucose metabolism.
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PMID:Inhibition of prostaglandin E2 catabolism and potentiation of hepatic prostaglandin E2 action in rat hepatocytes by inhibitors of oxidative metabolism. 316 76

Prostaglandin E2 (PGE2) and 16,16-dimethyl PGE2 were found to inhibit a hepatic glycogenolysis stimulated by epinephrine in the presence of propranolol (alpha 1-adrenergic response), isoproterenol (beta-adrenergic response) and glucagon in primary cultures of rat hepatocytes. The inhibitory effects to these stimulations were maximally increased (60-100%) in the cultures on day 2 or 3. Pretreatment of the cultured hepatocytes with pertussis toxin (islet-activating protein) resulted in a complete blockage of the prostaglandin-induced inhibition of glycogenolysis in a dose-dependent manner. Pertussis toxin had no significant effect on the glycogenolysis stimulated by these compounds in the absence of prostaglandin. The data suggest that the hepatic glycogenolysis stimulated by alpha 1- and beta-adrenergic responses and glucagon are modulated by the E series of prostaglandins via pertussis toxin-sensitive guanine nucleotide regulatory protein.
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PMID:Pertussis toxin blocks an inhibition of hormone-stimulated glycogenolysis by prostaglandin E2 and its analogue in cultured hepatocytes. 323 2

The influence of prostaglandins (PG) on central nervous system regulation of blood sugar homeostasis was studied in rats. Substances were injected into the third cerebral ventricle of anesthetized rats while rectal temperature and hepatic venous plasma glucose concentration were recorded. Stereotaxic microinjection of PGD2, E1, E2, and F2 alpha produced hyperglycemia and hyperthermia. The relative order of potency in hyperglycemia, PGF2 alpha greater than D2 greater than E1 greater than E2, was not consistent with that of hyperthermia, PGE2 greater than F2 alpha greater than E1 greater than D2, which suggests that hyperglycemia was a primary, not secondary, response to hyperthermia. Injection of PGF2 alpha caused a dose dependent (5-200 micrograms) increase in the hepatic venous plasma glucose level. Neither the injection of PGF2 alpha (50 micrograms) into the cortex nor into the systemic vein caused hyperglycemia. The injection of PGF2 alpha into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norephinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through the femoral vein completely prevented the increase of glucagon after administration of PGF2 alpha, although the increase of plasma glucose level was still observed. PGF2 alpha-induced hyperglycemia did not occur in adrenodemedullated rats. Intravenous injection of naloxone or propranolol did not affect the hyperglycemia, but phentolamine significantly prevented the hyperglycemic effect of PGF2 alpha. These results suggest that intraventricular PGF2 alpha affects the central nervous system to produce hyperglycemia by increasing epinephrine secretion from the adrenal medulla.
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PMID:Prostaglandins affect the central nervous system to produce hyperglycemia in rats. 347 43

The aim of this study was to determine whether food ingestion causes a change in the susceptibility of the stomach to dysrhythmia or in the characteristics of gastric dysrhythmia. The susceptibility of the stomach to develop dysrhythmia was measured by determining the median effective dose of four different drugs known to produce gastric dysrhythmia. These drugs were epinephrine, PGE2, met-enkephalin, and glucagon. The median effective dose for inducing gastric dysrhythmia was measured in four healthy conscious dogs by Dixon's up-and-down method during fasting and after feeding. The median effective dose of epinephrine, PGE2, met-enkephalin, and glucagon were higher after feeding (16.6, 16.6, 35.1, greater than 221 micrograms/kg, respectively) than during fasting (1.7, 5.2, 11.1, 61.0 micrograms/kg, respectively). The results indicate that feeding renders the stomach less susceptible to pharmacologically induced dysrhythmia. However, characteristics of gastric dysrhythmias, such as site of origin and direction of propagation, were similar whether they occurred during fasting or after feeding.
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PMID:Meal reduces sensitivity of the stomach to pharmacologically induced dysrhythmia. 347 88

Inhibited amino acid transport in skeletal muscle during sepsis has been demonstrated previously. In the present study we investigated the effects in vitro of plasma from septic animals or fractions of septic plasma that contain solutes with a molecular weight less than 30,000 daltons or less than 2000 to 3000 daltons on amino acid transport in incubated rat soleus (SOL) muscles. The influence of interleukin-1 (IL-1), prostaglandin E2 (PEG2), and the "catabolic" hormones corticosterone, glucagon, and epinephrine on muscle amino acid uptake was also investigated. Amino acid transport was studied with 3H-alpha-aminoisobutyric acid (AIB). Whole-septic plasma and the two low molecular-weight fractions of the septic plasma reduced muscle amino acid uptake by about 20%. IL-1 or PGE2 did not affect amino acid transport. When the catabolic hormones were added individually to incubated SOL muscles, no changes in AIB uptake were noticed. When glucagon or epinephrine was added in combination with corticosterone or when all three hormones were added together, amino acid transport was reduced by 10% to 15%. The results suggest that inhibited muscle amino acid uptake in sepsis is caused by a circulating factor(s) with a molecular weight less than 2000 to 3000 daltons. A synergistic action among the catabolic hormones may be one important factor for reduced muscle amino acid transport in sepsis.
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PMID:Reduced muscle amino acid uptake in sepsis and the effects in vitro of septic plasma and interleukin-1. 348 96

Insulin therapy was withdrawn from 15 well-controlled type I diabetic subjects for no longer than 18 h to examine the sequence with which 13,14-dihydro-15-keto-PGE2 (PGE-m), glucagon, norepinephrine, and epinephrine increased in circulating blood in diabetic subjects becoming ketoacidotic. Fourteen of 15 patients had increments in PGE-m; 12/12, 12/15, and 13/15 had increments in glucagon, norepinephrine, and epinephrine, respectively. Six of the 15 patients developed mild diabetic ketoacidosis (DKA) by 12-18 h; all had nonmeasurable C-peptide levels. This DKA group had significantly greater increments of PGE-m (835 +/- 130 versus 276 +/- 111 pg/ml, mean +/- SEM, P less than 0.01) but not glucagon, norepinephrine, or epinephrine compared with the 9 non-DKA patients. In the DKA group, there were significant PGE-m and glucagon increments in the circulation by 3 h, significant norepinephrine increments by 9 h, and epinephrine increments in 5/6 patients by 12 h (not statistically significant) of insulin withdrawal. These studies document that (1) PGE-m accumulates in the circulation during DKA, (2) PGE-m and glucagon increase before catecholamines, and (3) PGE-m, glucagon, and catecholamine levels promptly return to normal levels when insulin therapy is reinstituted. It is suggested that elevated PGE-m levels early in the onset of DKA may represent a host-defense mechanism.
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PMID:Prostaglandin E2 metabolite levels during diabetic ketoacidosis. 392 65


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