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 have shown that two unrelated prostaglandin antagonists block both thyrotropin (TSH) and prostaglandins E (PGE(1), PGE(2)) stimulation of thyroidal adenyl cyclase activation and cyclic 3',5'-adenosine monophosphate (cAMP) formation, suggesting that prostaglandins play an important role in regulating thyroid function. To further explore this postulate, we measured prostaglandin content by radioimmunoassay in homogeneous bovine thyroid cell preparations in the presence and absence of TSH. Antibodies to albumin-conjugated PGE(1) and PGF(2alpha) showed specificity for prostaglandins E and F, respectively, but reacted, albeit far less effectively, with heterologous prostaglandins. A double antibody system was used to separate free from antibody-bound PGE(1)-(3)H and PGF(2alpha)-(3)H. Thyroid cells were extracted with ethanol/ethyl acetate and the various prostaglandins separated on silicic acid columns. Recoveries of added PGE(1)-(3)H and PGF(2alpha)-(3)H through the extraction and separation procedures ranged from 50-80%. The sensitivity of the method was 10-50 pg. Basal thyroid cell content of PGE(1) and PGF(2alpha) "equivalents" varied between cell preparations (range = 2-6 ng/0.2 ml cell suspension) but, in each instance, remained constant during 5-30-min incubations at 37 degrees C. TSH, 10-100 mU/ml, increased the levels of cell PGE(1) and PGF(2alpha) "equivalents" 30-80% above basal during 5-15-min incubations. The stimulatory effect was specific for TSH, no increase in PGE(1) or PGF(2alpha) "equivalent" levels being seen with luteinizing hormone (LH), human growth hormone (HGH), adrenocorticotropic hormone (ACTH), or glucagon. These data support the thesis that prostaglandins may mediate TSH effects on thyroid.
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PMID:Thyrotropin increases prostaglandin levels in isolated thyroid cells. 462 70

Some metabolic effects of prostaglandins have been related to their alteration of adenosine-3',5'-monophosphate (cyclic AMP) metabolism in different tissues. Prostaglandins E1 and E2 stimulate liver adenylate cyclase in vitro, but conflicting reports have been made about metabolic changes caused by E prostaglandins in hepatic tissue. We have attempted to resolve these issues by comparing the effects of PGE1 with those of glucagon using broken-cell homogenates, intact hepatocytes, liver slices and perfused liver. Prostaglandin E1 (PGE1) increased cyclic AMP in liver slices and in perfused liver without increasing glycogenolysis, but PGE1 had no discernible effect on carbohydrate or cyclic AMP metabolism in isolated hepatocytes. Glucagon caused predictable increases in cyclic AMP and glycogenolysis using hepatocytes, liver slices or perfused liver. These data can be explained by the absence of PGE effects on cyclic AMP metabolism in hepatocytes. The concentration of E prostaglandins (PGEs) increased 1.75-fold during incubations (37 degrees C) of hepatocyte suspensions, but cyclic AMP remained constant. Addition of exogenous arachidonate and indomethacin to cell suspensions increased and decreased PGEs, respectively, but cyclic AMP and glycogen metabolism were unchanged. Arachidonate and indomethacin likewise did not alter glucagon-stimulated glycogenolysis or cyclic AMP biosynthesis. The production of E prostaglandins and cyclic AMP appears to be unrelated in hepatocytes.
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PMID:Dissociation of E prostaglandin effects on liver glycogenolysis and cyclic AMP levels. 631 5

Prostaglandins of the E series are implicated as regulators of glucose homeostasis because of their effects on glucose production and secretion of insulin and glucagon. PGE is postulated to play a role in the pathophysiology of insulin secretion in adult-onset (Type II) diabetes mellitus. Evidence supporting this hypothesis includes the demonstration that PGE inhibits glucose-induced acute insulin responses in normal humans. Moreover, drugs that inhibit synthesis of PGE improve abnormal insulin secretion in human subjects with Type II diabetes mellitus.
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PMID:Prostaglandins, glucose homeostasis, and diabetes mellitus. 634 49

The effect of E-series prostaglandins (PGE) on hepatic glucose metabolism is controversial. This study uses isolated rat hepatocytes and exogenously added PGE analogs or frequent native PGE additions (to compensate for hepatic PGE degradation) to define PGE's effect on hepatic glycogenolysis. 16,16-Dimethyl PGE2, 15(S),15-methyl PGE2, PGE1 and PGE2 all inhibit glucagon-stimulated glycogenolysis. It is concluded that E-series prostaglandins can act directly on the liver to inhibit glycogenolysis.
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PMID:Inhibition of glucagon-stimulated hepatic glycogenolysis by E-series prostaglandins. 658 8

Experimental evidence has recently accumulated indicating that administration of some prostaglandins (PGs), particularly those of the E series, can evoke release of glucagon by the pancreatic alpha-cells. Virtually, all the in vitro studies (isolated perfused rat pancreas, isolated guinea-pig islets) agree that PGs can increase both basal and stimulated glucagon release. On the other hand, inhibition of PG synthesis with indomethacin blocks glucagon release. In rats and in normal humans, PGE1, but not PGA2 or PGF2a, causes a progressive rise of plasma glucagon levels. While in the rat this response seems independent of the adrenergic nervous system, in man the hyperglucagonemia induced by PGE1 is easily suppressed by propranolol, suggesting an interaction between the prostaglandin and the beta-receptors of the alpha-cell. Studies with inhibitors of PG synthesis in vivo have yielded conflicting results, depending on the particular experimental protocol used and on the type of inhibitor tested. In normal humans, it seems that acetylsalicylic acid (ASA) has no effect on glucagon response to arginine, tolbutamide and insulin-induced hypoglycemia. Conversely, a stimulator of PG synthesis, such as furosemide, increases glucagon response to an arginine pulse in man. In insulin-dependent diabetics, who present an exaggerated glucagon response to stimulants, ASA fails to alter glucagon response to arginine, but completely blunts the glucagon response to salbutamol, a weak beta-2 receptor agonist. In conclusion, these observations provide evidence in support to a role for PGs, at least PGE, in the contro of glucagon release.
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PMID:Prostaglandins and the alpha-cell. 701 76

Open (OC) or laparoscopic (LC) cholecystectomy is considered a relative contraindication in patients with liver cirrhosis. The effect of LC and OC on the hepatic catabolic stress response was studied in patients with postnecrotic liver cirrhosis and chronic hepatitis to define the most suitable procedure from a metabolic point of view. Altogether 14 patients with cirrhosis and 14 with chronic hepatitis were randomized to LC or OC (n = 7 in each group). The increase in the functional hepatic nitrogen clearance (FHNC) was quantified. Changes in glucose, insulin, glucagon, cortisol, epinephrine, norepinephrine, and prostaglandin E(2) (PGE(2)) were observed. There was no difference in FHNC between LC and OC in any of the patients. Among cirrhotic patients OC caused a 132% increase in FHNC (p < 0.05) and among the hepatitis patients a 69% increase (p < 0.05). In contrast, there was no significant increase following LC in any of the patients. OC increased fasting glucose and insulin in the hepatitis patients (p < 0.01 and p < 0.001, respectively) and in the cirrhosis group (p < 0.01 and p < 0.05, respectively). Alanine stimulation increased glucose in hepatitis patients after OC (p < 0.05) and after LC (p < 0.01). Stimulated glucagon increased after OC in the hepatitis group (p < 0.05). During stimulation cortisol was higher following LC in hepatitis patients (p < 0.01) and cirrhotic patients (p < 0.05). Fasting PGE(2) was down-regulated after LC in hepatitis patients (p < 0.05) and cirrhotic patients (p < 0.01) and after OC in the hepatitis group (p < 0.001). FHNC is similar after LC and OC. Thus from a metabolic point of view, LC has no advantage over OC.
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PMID:Postoperative hepatic catabolic stress response in patients with cirrhosis and chronic hepatitis. 1065 74

We investigated the effect of adenovirally mediated overexpression of adenylyl cyclase type 6 (AC6), a major form of AC expressed in mammalian heart, on G protein-coupled receptor regulation of cAMP production in neonatal rat ventricular myocytes. Following gene transfer of AC6, isoproterenol- and forskolin-stimulated increases in cAMP were markedly enhanced, whereas basal levels of cAMP and responses to several other agonists that stimulate cAMP formation, e. g., prostaglandin E(2) (PGE(2)), H(2) agonist, glucagon, and A(2) agonist were not increased. Studies to test whether the selective enhancement in beta-adrenergic receptor (AR) response might result from inhibition of AC6 by Galpha(i) and Gbetagamma indicated that pertussis toxin-sensitive inhibition by the muscarinic cholinergic agonist carbachol was unaltered in myocytes overexpressing AC6. Pertussis toxin treatment failed to reveal an enhancement by AC6 overexpression of basal or PGE(2)-stimulated cAMP. Immunoblot analysis of membrane fractions indicated that beta(1)-AR and AC6 are expressed in fractions enriched in caveolin-3 and morphologic caveolae. The data suggest that loss of G(i)-mediated inhibition is not the mechanism for enhancement of beta-AR-stimulated cAMP formation and that key components of beta-AR-mediated activation of AC exist in caveolae of cardiac myocytes, providing a means by which beta-AR response is selectively enhanced by increasing AC6 expression.
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PMID:Selective enhancement of beta-adrenergic receptor signaling by overexpression of adenylyl cyclase type 6: colocalization of receptor and adenylyl cyclase in caveolae of cardiac myocytes. 1077 94

The cellular distribution of Ca(2+)-inhibitable adenylyl cyclase (AC) type 5 and type 6 mRNAs in rat outer medullary collecting duct (OMCD) was performed by in situ hybridization. Kidney sections were also stained with specific antibodies against either collecting duct intercalated cells or principal cells. The localization of type 5 AC in H(+)-ATPase-, but not aquaporin-3-, positive cells demonstrated that type 5 AC mRNA is expressed only in intercalated cells. In contrast, type 6 AC mRNA was observed in both intercalated and principal cells. In microdissected OMCDs, the simultaneous superfusion of carbachol and PGE(2) elicited an additive increase in the intracellular Ca(2+) concentration, suggesting that the Ca(2+)-dependent regulation of these agents occurs in different cell types. Glucagon-dependent cAMP synthesis was inhibited by both a pertussis toxin-sensitive PGE(2) pathway (63.7 +/- 4.6% inhibition, n = 5) and a Ca(2+)-dependent carbachol pathway (48.6 +/- 3.3%, n = 5). The simultaneous addition of both agents induced a cumulative inhibition of glucagon-dependent cAMP synthesis (78.2 +/- 3.3%, n = 5). The results demonstrate a distinct cellular localization of type 5 and type 6 AC mRNAs in OMCD and the functional expression of these Ca(2+)-inhibitable enzymes in intercalated cells.
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PMID:Cellular localization of type 5 and type 6 ACs in collecting duct and regulation of cAMP synthesis. 1089 1

Inhibition of prostaglandin synthesis by the drug indomethacin suppresses the synthesis of the cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), and leads to a metabolic state comparable to type II diabetes. It was of interest whether prostaglandin-deficiency likewise causes sensitization of adenylyl cyclase, as this has been reported for the diabetic state. In liver plasma membranes of indomethacin-treated male rats, basal and forskolin-stimulated cyclic AMP synthesis remained unchanged when compared to untreated control rats. In control rats, stimulation of cyclic AMP synthesis by fluoride (2.2-fold) or glucagon (3.5-fold) was much lower than stimulation by forskolin (6.6-fold). In contrast, in indomethacin-treated rats, stimulation of cAMP synthesis by fluoride (4.6-fold) or glucagon (5.2-fold) nearly matched the stimulation by forskolin (6.4-fold). The level of alpha1-adrenergic receptors was slightly reduced, from 450 to 320 fmol/mg protein, by the indomethacin treatment. Independent of the treatment by indomethacin, stimulation of cyclic AMP synthesis by adrenaline failed, in agreement with the low density of adrenergic beta-receptors. In conclusion, PGE deficiency sensitizes adenylyl cyclase in rat liver for G protein-coupled receptors (glucagon) and also for fluoride.
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PMID:Prostaglandin deficiency promotes sensitization of adenylyl cyclase. 1093 86

Rats exposed to stress developed various changes in the gastrointestinal tract and hormones. The present study was designed to compare the impact of tocopherol and tocotrienol on changes that influence gastric and hormonal parameters important in maintaining gastric mucosal integrity in rats exposed to restrain stress. These include gastric acidity, gastric tissue content of parameters such as malondialdehyde, prostaglandin (PGE(2)), serum levels of gastrin and glucagon-like peptide-1 (GLP-1). Sixty male Sprague-Dawley rats (200-250 g) were randomly divided into three equal sized groups, a control group which received a normal rat diet (RC) and two treatment groups each receiving a vitamin deficient diet with oral supplementation of either tocopherol (TF) or tocotrienol (TT) at 60 mg/kg body weight. Blood samples were taken from half the number of rats (non-stressed group) after a treatment period of 28 days before they were killed. The remaining half was subjected to experimental restraint-stress, at 2 hours daily for 4 consecutive days (stressed groups), on the fourth day, blood samples were taken and the rats killed. The findings showed that the gastric acid concentration and serum gastrin level in stressed rats were significantly (P<0.05) reduced compared to the non-stressed rats in the control and TF groups. However, the gastric acidity and gastrin levels in the TT group were comparable in stressed and non-stressed rats. These findings suggest that tocotrienol is able to preserve the gastric acidity and serum gastrin level which are usually altered in stressed conditions. The PGE(2) content and the plasma GLP-1 level were, however, comparable in all stressed and non-stressed groups indicating that these parameters were not altered in stress and that supplementation with TF or TT had no effect on the gastric PGE2 content or the GLP-1 level. The malondialdehyde, an indicator of lipid peroxidation was higher from gastric tissues in the stressed groups compared to the non-stressed groups. These findings implicated that free radicals may play a role in the development of gastric injury in stress and supplementation with either TF or TT was able to reduce the lipid peroxidation levels compared to the control rats. We conclude that both tocopherol and tocotrienol are comparable in their gastro-protective ability against damage by free radicals generated in stress conditions, but only tocotrienol has the ability to block the stress-induced changes in the gastric acidity and gastrin level.
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PMID:A comparison between tocopherol and tocotrienol effects on gastric parameters in rats exposed to stress. 1632 42


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