Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An immortalized cell line, called P9, was derived from hepatocytes by transfection with SV40 DNA. These cells expressed enzyme activities characteristic of hepatocytes, namely glucose-6-phosphatase, glycogen phosphorylase, bilirubin glucuronyltransferase and both glucagon- and prostaglandin E1 (PGE1)-stimulated adenylate cyclase activities, albeit at decreased levels compared with native hepatocytes. Levels of the G-protein subunits alpha-Gi-2, alpha-Gi-3, G beta and the 'long' form of alpha-G2 (45 kDa) were approximately 4-fold higher relative to native hepatocytes, whereas those of the 'short' form of alpha-G2 (42 kDa) were lower by approximately 40%. Associated with this were marked alterations in the guanine nucleotide regulation of adenylate cyclase. Receptor-mediated stimulation, achieved by either PGE1 or glucagon, was apparent in P9 cells, although the latter was only evident upon amplification with forskolin. Glucagon-stimulated cyclic AMP accumulation in P9 cells did not exhibit desensitization, as in hepatocytes, nor was the phosphorylation of alpha-Gi-2 evident. Culture of P9 cells with insulin led to a dose-dependent decrease (EC50 0.2 +/- 0.1 nM) in the ability of PGE1 to stimulate adenylate cyclase activity, with the maximum effect attained after approximately 6 h. A comparable attenuation of stimulation was seen for glucagon- and guanine-nucleotide-stimulated adenylate cyclase activities. In cells cultured with insulin, lower levels of GTP were required to stimulate adenylate cyclase, ADP-ribosylation of the 45 kDa form of alpha-Gs with cholera toxin was attenuated, and the expression of both alpha Gi-2 and alpha-Gi-3 was increased. It is suggested that the expression of alpha-Gi-2 and alpha-Gi-3 may be directly regulated by the action of insulin in hepatocytes and P9 cells.
 ...
PMID:Analysis of the adenylate cyclase signalling system, and alterations induced by culture with insulin, in a novel SV40-DNA-immortalized hepatocyte cell line (P9 cells). 801 Sep 67

Effects of prostaglandin (PG) E1 on ischemia-reperfusion (I-R) injury to the pancreas was evaluated using isolated in vivo perfused dog pancreas. Pancreatic endocrine and exocrine functions were stimulated with 10(-12) M cholecystokinin octapeptide (CCK-8). This amount of CCK-8 promoted production of insulin, glucagon, PGI2, and thromboxane (Tx) A2 in the pancreas. Sixty minutes of ischemia and subsequent reperfusion induced damage to pancreatic ductular, acinar, and beta cells. Intra-arterial administration of PGE1 at a dose of 0.5 microgram/kg/min throughout the experiment prevented the I-R injury, reducing plasma lipid peroxides, and elevating PGI2 without changing TxA2 in the pancreas. PGE1 thus appears to protect pancreatic function from I-R injury both by depressing the effect of free-radicals and by decreasing TxA2/PGI2 which predicts cell injury.
 ...
PMID:Prostaglandin E1 protects dog pancreas from ischemia-reperfusion injury. 802 58

The aim of the study was to investigate the effect of aging on cytoprotective properties of prostaglandins. Hepatocytes were obtained by collagenase perfusion of livers of young (4-6 mo) and old (24-28 mo) male Wistar rats. Cells were incubated for 1.5 h in Krebs-Ringer-bicarbonate buffer containing glucose and 3H-leucine in the presence of galactosamine (2.5-100 mM), PGE1, or two prostacyclin analogues: 9 beta-methylcarbacyclin and TRK-100. Cell damage was assessed by decrease in the rate of protein synthesis measured as 3H-leucine incorporation into acid precipitable material, and by increase in lactate dehydrogenase release into the medium. Hepatocytes from old rats were more susceptible to suppression of protein synthesis by GalN than cells of young ones. Preincubation of cells for 15 min with 9MC (41-560 nM) or PGE1 (10-100 nM), but not with TRK-100, before adding 10 mM GalN, led to a partial recovery of protein synthesis in both age groups. GalN increased LDH release and decreased ATP/ADP ratio to a similar extent in hepatocytes of young and old rats; both parameters were not altered by preincubation of cells with PGs. PGE1 and 9MC, but not TRK-100, elevated cyclic AMP content in hepatocytes of young but not old rats. Glucagon and forskolin similarly increased cyclic AMP content in cells of both young and old animals. These in vitro results suggest that PGE1 and some prostacyclin analogues might protect hepatocytes of both young and old rats from chemical damage, and stress the necessity for further research on cyto- and hepato-protection in the elderly.
 ...
PMID:Prostaglandin cytoprotection of galactosamine-incubated hepatocytes isolated from young and old rats. 803 Aug 38

Studies were carried out to investigate the effects of prostaglandin E1 (PGE1) pretreatment on normothermic liver ischemia. Mixed-breed dogs were divided into three groups: a control group, a group with induced liver ischemia, and a group pretreated with PGE1 followed by induced liver ischemia. Liver ischemia was induced by the Pringle procedure for 60 min. PGE1 was administered intravenously to some dogs at a dose of 0.5 microgram/kg/min for 30 min prior to the Pringle procedure. Sham operations were performed without induction of liver ischemia in control animals. Insulin, glucagon, and glucose metabolic clearance rates were examined before and after the Pringle procedure in the control and experimental groups. Insulin and glucose metabolic clearance rates decreased 5 min after declamping in the ischemic group, while the glucagon metabolism was not affected, and lipid peroxide production increased. In contrast, hepatic insulin metabolism improved, and lipid peroxide production normalized in the ischemic group which was pretreated with PGE1. This study suggests that PGE1 prevents hepatic metabolic disturbances due to warm ischemia and subsequent reperfusion.
 ...
PMID:Prostaglandin E1 protects liver from ischemic damage. 807 86

Hepatocytes isolated from rats by the collagenase perfusion method were cultured as monolayers at concentrations of 0.4-1.1 x 10(6) attached cells/dish (9 cm2) for 1-3 days and the effect of prostaglandins on their glycogenolysis was studied. By use of [14C]glycogen-labeled cells, prostaglandin E2 (PGE2) was found to have a stimulatory effect on glycogen degradation at high cell density (more than 0.8 x 10(6) cells/dish) in 1-day cultures. PGE2 was maximally effective at 10(-7) M, increasing [14C]release from cellular [14C]glycogen to 2-3 times the basal level after 1 h incubation, and to plateau level within 2 h. PGE1, 16,16-dimethyl PGE2 and PGF2 alpha had similar effects, but PGD2 and dinor-PGE1 (a metabolite of PGE1 and PGE2 in hepatocytes) had no effect. This prostaglandin-induced glycogen degradation was observed in 1-day cultures, with a maximum between 20-30 h, but not in 2-day and later cultures. Treatment of hepatocytes with pertussis toxin potentiated PGE2-stimulated glycogen degradation, indicating that the effect involves a different pathway from that for inhibition of glucagon- and epinephrine-stimulated glycogenolysis by E series prostaglandins reported previously.
 ...
PMID:Stimulation of glycogen degradation by prostaglandin E2 in primary cultured rat hepatocytes. 832 15

In this study we have examined the effects of variations of the plasma membrane phospholipid and cholesterol content on the metabolic functions of the adenylyl cyclase complex in intact cells. Exposure of cells to 0.1 U/ml of sphingomyelinase led to the degradation of 75, 55 and 40% of the cellular total sphingomyelin mass in human skin fibroblasts (HSF), Chinese hamster lung fibroblasts (CHLF) and rat liver hepatocytes (RLH), respectively. Degradation of sphingomyelin in native cells led in turn to a reduction (within 60 min) of the plasma membrane cholesterol content (by 25, 15 and 10%, respectively). This manipulation of the plasma membrane lipid content did not affect the forskolin or prostaglandin E1-induced activation of adenylyl cyclase (as measured from the conversion of [3H]adenine via [3H]ATP to [3H]cAMP). These manipulations did, however, increase the basal rate of [3H]cAMP formation in rat liver hepatocytes (but not in the fibroblast cell types). With Chinese hamster lung fibroblasts, transfected to express an alpha 2-adrenergic receptor, it was observed that the alpha 2-adrenergic receptor-induced inhibition of adenylyl cyclase activity was slightly (but significantly) diminished in sphingomyelin and cholesterol-depleted cells. With isolated rat liver hepatocytes it was observed that the glucagon (receptor) mediated activation of adenylyl cyclase was also reduced in sphingomyelinase-treated cells. In another set of experiments, CHLF and RLH cells were exposed for 2 h to vesicles prepared from dilauroylphosphatidylcholine, to increase the lateral packing density in the outer leaflet of the plasma membrane. In such treated cells, the receptor-coupling to adenylyl cyclase was markedly reduced both in CHLF (the alpha 2-adrenergic receptor) and RLH (the glucagon-receptor) cells. We conclude that the direct activation of adenylyl cyclase (i.e., by forskolin) is not markedly affected by manipulations outer leaflet phospholipid composition (either reduction of sphingomyelin or increase of phosphatidylcholine), whereas receptor-coupled events clearly are.
 ...
PMID:Effects of the phospholipid environment in the plasma membrane on receptor interaction with the adenylyl cyclase complex of intact cells. 838 66

A rare case of severe acute hepatitis A complicated by pure red cell aplasia (PRCA) is reported. A 60-year-old man with jaundice and hepatomegaly was diagnosed as having acute hepatitis A by positive IgM anti-hepatitis A antibody (anti-HAV). Severe anemia rapidly developed 3 weeks after admission, and the patient was diagnosed with PRCA by both bone marrow smears and erythrocyte survival study. The anemia was transient and bone marrow recovered within 1 week. However, concomitant with bone marrow recovery, the hepatitis worsened. He became drowsy and disoriented and severe jaundice, ascites, prolonged prothrombin time, increased transaminase levels, and abnormal electroencephalogram (EEG) were exhibited. Plasma exchange transfusion and glucagon-insulin (GI) therapy improved the consciousness level, but bilirubin, transaminase levels, and IgM anti-HAV titer remained high. Intravenous administration of lipophilized prostaglandin E1 (lipo-PGE1) was added to the GI therapy. Bilirubin and transaminase levels were normalized in the 8th week after the initiation of this combination therapy (17 weeks after admission). The combined use of lipo-PGE1 with plasma exchange and GI therapy appeared to be useful for the prolonged severe hepatitis in this patient.
 ...
PMID:Severe acute hepatitis A associated with acute pure red cell aplasia. 884 89

Rats were rendered diabetic by streptozotocin, after which serum glucose-dependent insulinotropic polypeptide (GIP) levels, duodenal mucosal GIP content, and GIP mRNA levels were nine times, 50% and 80%, respectively, greater than in control rats. To determine whether an increase in GIP gene expression might induce chronic desensitization of its receptor, normal rats were subjected to continuous intravenous GIP infusion. Serum GIP levels increased gradually in GIP-infused rats, and by 4 h a threefold increase was detected. In response to GIP infusion, the serum insulin concentration increased at 30 min, followed by a gradual decrease, and at 4 h, no increase in insulin levels was detected despite a sustained elevated serum GIP level. The response to glucagon-like peptide-1 (GLP-1) was preserved, a reporter cell line (LGIPR2) stably transfected with rat GIP receptor cDNA was studied. GIP stimulated adenosine 3', 5'-cyclic monophosphate (cAMP) production in LGIPR2 cells, which was first detected after 1 h of stimulation, reached maximum level at 4 h, and returned to basal concentrations by 16 h. Additional stimulation with GIP at 16 h did not affect cAMP generation, indicating desensitization of the GIP receptor by the ligand. In contrast, a response to prostaglandin E1 or forskolin in GIP-desensitization was a receptor-specific process. The results of these studies indicate that GIP gene expression is enhanced in diabetic animals and that elevated serum GIP level induces chronic desensitization of the GIP receptor in vivo and in a stably transfected cell line.
 ...
PMID:Chronic desensitization of the glucose-dependent insulinotropic polypeptide receptor in diabetic rats. 892 74

We characterized the proliferative action of prostaglandins (PGs) in relation to their membrane receptors on rat hepatocytes in primary culture. PGs in the order 16,16-dimethyl PGE2 > PGE2 > PGF2alpha >> PGD2 augmented epidermal growth factor (EGF)/insulin-induced DNA synthesis, assessed by [(3)H]thymidine incorporation, in a concentration-dependent manner, whereas PGs alone did not stimulate basal DNA synthesis without EGF and insulin. The cells exhibited [(3)H]PGE2 binding sites that were displaced by unlabeled PGs in the order PGE1 = PGE2 > PGF2alpha > PGD2. PGE2 inhibited glucagon-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation concentration dependently. The mean effective concentration for DNA synthesis, median inhibitory concentration for cAMP accumulation, and dissociation constant for [(3)H]PGE2 binding at 25 degrees C were almost identical (approximately 70 nM). Treatment of the cells with pertussis toxin (100 ng/ml), which ADP-ribosylated most of the 41-kDa substrate, abolished the proliferative effects of PGs. We detected the expression of mRNA of the EP3 subtype PGE2 receptor using reverse transcription-polymerase chain reaction. Moreover, an EP3 agonist, enprostil, but not the EP1 agonist 17-phenyl-trinor-PGE2 or the EP2/EP4 agonist 11-deoxy-PGE1, stimulated EGF/insulin-induced DNA synthesis. These results indicate that PGs act as comitogenic growth factors through the EP3 subtype PGE2 receptor coupled with G(i) protein in cultured rat hepatocytes.
 ...
PMID:Prostaglandins induce proliferation of rat hepatocytes through a prostaglandin E2 receptor EP3 subtype. 912 80

Prostaglandins of the E (PGE) series have long been considered "catabolic" hormones, but recent data suggest that they may be secreted in critically ill patients to counteract stress hormones, stimulating protein synthesis. Their use is under scrutiny to improve hepatic microcirculation and as cytoprotective agents. We tested the effects of PGE1 on hepatic and whole-body nitrogen metabolism in eight patients with cirrhosis. Urea-nitrogen synthesis rate, alpha-amino-nitrogen levels, and nitrogen exchange were measured in the basal, postabsorptive state and in response to continuous alanine infusion, in paired experiments, during superinfusion of PGE1 or saline. Splanchnic and systemic hemodynamics were assessed by echo-Doppler at the beginning and at the end of each experiment. PGE1 produced a rapid fall in plasma amino acids and in urea-nitrogen synthesis rate, as well as a positive nitrogen exchange. The slope of the regression of alpha-amino-nitrogen levels on urea-nitrogen synthesis rate, a measure of liver cell metabolic activity, was not affected, but the regression line was shifted rightward, suggesting a nitrogen-sparing effect of PGE1. Mesenteric artery and portal flow were unchanged, whereas femoral artery flow increased by 30%. Insulin and glucagon levels were not systematically different. We conclude that PGE1 reduces hepatic urea synthesis rate, independent of hormones and/or hepatic flow, possibly acting at the peripheral level on amino acid transport, thus reducing amino acid supply to the liver. The resulting net nitrogen sparing might be the basis for the beneficial effect of PGE1 in clinical hepatology.
 ...
PMID:Effects of systemic prostaglandin E1 on hepatic amino acid-nitrogen metabolism in patients with cirrhosis. 950 Jul 12


<< Previous 1 2 3 4 5 6 7 8 9 10