Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:034761 (insulin)
 211,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels of glucose, insulin, and glucagon in portal vein plasma and of liver glycogen and cyclic AMP and activities of glycogen synthase and phosphorylase in liver were assayed in control (CONT) rats and rats infected (INF) with Diplococcus pneumoniae. In INF rats compared with CONT rats, insulin and glucagon levels were higher (8,12,24 h). Activity of synthase I was lower (8, 12, 24 h) and of phosphorylase higher (12 and 24 h) in INF rats. Cyclic AMP levels were higher in INF rats at 12 and 24 h. Total synthase activity was lower in INF rats at 24 h. Glucose given intravenously increased glycogen less in INF than in CONT rats and activated synthase and inactivated phosphorylase in all animals except at 24 h in INF rats. However, in situ perfusion of the livers at 24 h with glucose in buffer decreased phosphorylase activities in all animals and increased synthase I activities in CONT but not INF rats.
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PMID:Altered hepatic glycogen metabolism and glucoregulatory hormones during sepsis. 0 97

The NA-K-ATPase of toad skin was characteristically sensitive to Na, K, and ATP. It was not affected by amiloride, vasopressin, cAMP, and thyroxine, but stimulated by insulin. Ouabain, a potent inhibitor at 37 degrees C, did not inhibit the enzyme activity significantly at 23 degrees C. The optimal pH for the enzyme activity increased as temperature decreased. However, the optimal OH-/H+ ratio of the medium remained constant at 16 regardless of temperature. The Km for ATP remained unchanged between 37 and 8 degrees C if the OH-/H+ ratio was held constant at 16, but increased as temperature decreased if the pH of the medium was held constant at 7.4. The enzyme activity showed no appreciable variation between 37 and 20 degrees C with a constant OH-/H+ ratio of 16, whereas it decreased logarithmically at a constant pH of 7.4 over the same temperature range. These results indicate the presence of a typical Na-K-ATPase system in toad skin and that the enzyme is in the most active catalytic state at a fixed level of OH-/H+ ratio in the medium regardless of incubation temperature.
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PMID:Properties of toad skin Na-K-ATPase with special reference to effect of temperature. 1 98

Chick liver cell monolayers synthesize fatty acids at in vivo rates and are responsive to insulin and glucagon. High rates of fatty acid synthesis are maintained with insulin present and lost slowly without insulin. Glucagon or 3',5'-cyclic AMP cause immediate cessation of fatty acid synthesis. The site of inhibition appears to be cytoplasmic acetyl-CoA carboxylase which catalyzes the first committed step of fatty acid synthesis. Liver carboxylase exists either as catalytically inactive protomers or active filamentous polymers. Citrate, an allosteric activator of the enzyme, is required for both catalysis and polymerization. Glucagon and cAMP cause an immediate decrease in the cytoplasmic citrate concentration of chick liver cells apparently by inhibiting the conversion of glucose to citrate at the phosphofructokinase reaction. Since fatty acid synthesis and citrate level are closely correlated, citrate appears to be a feed-forward activator of the carboxylase in vivo. Compelling evidence indicates that carboxylase filaments are present in the intact cell when citrate levels are high and depolymerize when citrate levels fall. Hence, carboxylase activity and fatty acid synthetic rate appear to be determined by cytoplasmic citrate level.
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PMID:Hormonal regulation of acetyl-CoA carboxylase activity in the liver cell. 4 83

This study was aimed at evaluating the effect of theophylline, a drug that increases the intracellular concentrations of cAMP by inhibiting phosphodiesterase activity, on somatostatin (SRIF)-mediated inhibition of insulin secretion in man. Acute insulin response (AIR) to i.v. glucose (mean change 3-10 min) was almost totally suppressed by SRIF (500 micrograms/h) and glucose utilization was reduced (p less than 0.0001). These SRIF-induced decreases failed to be eliminated by a concurrent infusion of theophylline (100 mg as a loading dose followed by a constant infusion of 5 mg/min). Theophylline alone resulted in a significant increase in both AIR (p less than 0.01) and glucose removal rates (p less than 0.05). Thus, our data disprove the involvement of the phosphodiesterase enzymes in the inhibitory action of SRIF on glucose-induced insulin secretion in man.
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PMID:Somatostatin and insulin secretion in man. II. The effect of theophylline. 4 65

Isolated pancreatic islets of noninbred ob/ob mice were used to test the hypothesis that adenylate cyclase responds to changes of the transmembrane milieu or electric field in intact beta-cells. In the presence of a phosphodiesterase inhibitor, ouabainstimulated both the release of insulin and the islet content of cAMP. Ouabain had no noticeable effect on the islet content of cGMP. These results support the hypothesis at test. However, because ouabain also had some stimulatory effect on cAMP in islet homogenates, a direct action of ouabain on adenylate cyclase cannot be ruled out.
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PMID:Effects of ouabain on insulin release, adenosine 3',5'-monophosphate and guanine 3',5'-monophosphate in pancreatic islets. 8 35

Drug-induced porphyrin accumulation occurs in chick embryo liver cells maintained in serum-free Waymouth MD 705/1 medium. Addition of insulin and thyroxine to the medium results in a marked enhancement of porphyrin accumulation. The addition of hydrocortisone results in a further enhancement of porphyrine accumulation. Several agents which are reported to increase intracellular adenosine 3':5'-monophosphate (cAMP) levels, viz. glucagon, sodium fluoride, cAMP or its dibutyryl derivative, 3-isobutyl-1-methylxanthine and papaverine enhanced drug-induced porphyrin biosynthesis. On the other have, agents which are reported to decrease intra-cellular cAMP levels, viz. alloxan and imidazole, diminished drug-induced porphyrin accumulation. cAMP appears to enhance, but not to function as a "second messenger" in drug-induced porphyrin biosynthesis. Drug-induced porphyrin accumulation in chick embryo liver cells depend upon the insulin to glucagon ratio. A low level of porphyrin accumulation occurs at insulin to glucagon ratios similar to those found following glucose administration in vivo, suggesting a possible explanation for the therapeutic effect of glucose in hepatic porphyria. The 5 alpha A(A:B trans) and 5 beta H(A:Bcis) steroids are equipotent in inducing delta-aminolevulinic acid synthetase and porphyrin accumulation in chick embryo liver cells maintained in serum-free culture medium. Thus, there is no specific steric requirement for porphyrin-inducing activity in steroids.
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PMID:Hormonal effects on the regulation of hepatic heme biosynthesis. 8 65

The isolated hepatocyte preparation (from 24-hour fasted rats) comprised a homogeneous population of intact cells as shown by electron microscopy. Homogenates of hepatocytes were incubated for 10 minutes in an ionic buffer solution containing 1.5% gelatin with and without hormones and centrifuged at 27,500 X g for 30 minutes, and the supernatant fractions were assayed for enzyme activities. Hexokinase activity was absent, although it was easily detectable in the same fraction of intact liver. The activity of glucokinase was uninfluenced by any of the hormones. The assayable activity of fructose diphosphatase was not increased by glucagon, monobutyryl cyclic adenosine-3',5'-monophosphate (mb-cAMP), or epinephrine, nor was it inhibited by insulin. The activities of phosphofructokinase and pyruvate kinase were not increased by insulin; however, glucagon and mb-cAMP inhibited the assayable activity of phosphofructokinase and pyruvate kinase to 20 to 25% of control values. Epinephrine did not influence the assayable activity of either enzyme, although it stimulated gluconeogenesis as markedly as did glucagon and mb-cAMP. When liver cell homogenates were subjected to centrifugation at higher forces (37,400 X g for 60 minutes or greater), the assayable activity of phosphofructokinase in supernatant fractions began to diminish. Additional loss of phosphofructokinase activity was observed in supernates prepared from cells that had been incubated with epinephrine; however, in these supernatant fractions, pyruvate kinase activity did not differ from control values. The results reported here demonstrate (1) a behavior of phosphofructokinase which is not predictable on the basis of its known solubility properties, and (2) differential effects of glucagon and epinephrine on the activity of phosphofructokinase which suggest that separate mechanisms are operative in stimulation of glucoeogenesis by glucagon and epinephrine.
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PMID:Gluconeogenesis in isolated rat hepatic parenchymal cells. IX. Differential effects of glucagon and epinephrine on phosphofructokinase and pyruvate kinase. 13 35

Smooth muscle cells were grown from thoracic aortas of 1-year-old monkeys (Macaca nemistrina). The effect of insulin on the proliferation of these cells was studied by comparing the growth of cells in culture medium to which insulin had been added with that of cells in basal (1% monkey serum) medium and in growth-promoting 5% monkey serum. Insulin in concentrations of 10, 100, 1,000, and 10,000 muunits/ml resulted in successively greater stimulation of growth which was highly significant (P smaller than 0.001) by analysis of variance. There was a significant linear relationship between the logarithm of the insulin dose and cell growth. However, the highest concentration of insulin produced only 50% of the effect of 5% monkey serum. Serum from which insulin had been removed stimulated growth less well (P smaller than 0.05) than did untreated serum at the same concentration (5%) but had significant (P smaller than 0.05) stimulating properties compared with whole serum at a lower concentration. Cells that were older in culture life (eight or nine passages) did not show a growth response to insulin and had an attenuated response to 5% serum. The effect of insulin (100 muunits/ml) was inhibited by dibutyryl cyclic adenosine monophosphate (db-cAMP) (5 times 10-5 M), although there was a latent period of 3 days before inhibition occurred; db-cAMP had no effect on cell counts in the absence of insulin. The electron microscopic appearance of the cells was unaltered by insulin.
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PMID:Effect of insulin on the proliferation of cultured primate arterial smooth muscle cells. 16 9

Concomitant with glucose-induced insulin release, there occurred an increase of ATP from 4.40 plus or minus 0.21 to 23.16 plus or minus 0.52 pmol/100 islets/min (P less than 0.001) in the effluent from perifused rat islets. There is a linear relationship between circulating ATP and insulin levels both in the stimulated and basal state (r = 0.689, P less than 0.01). Islets incubated with labeled adenine for a short period of time (37.5 min) showed no release of radioactivity upon subsequent glucose-induced insulin release. Islets incubated for a prolonged interval with labeled adenine (150 min) showed an increase in acid soluble radioactivity in the effluent during glucose-induced insulin release. Following incubation of the islets with labeled adenine for 150 min, approximately 5% of the homogenate radioactivity was found in the secretory granules. Using column chromatography to separate the adenine nucleotides, the distribution of radioactivity among the various nucleotides in the secretory granule fraction was found to be: AMP 54.42 plus or minus 4.96%, ADP 14.20 plus or minus 1.63%, ATP 15.39 plus or minus 3.84%, and cAMP 16.07 plus or minus 2.11%. The distribution of radioactivity in the effluent adenine nucleotides after glucose-induced insulin release was: AMP 32.83 plus or minus 4.62%, ADP 24.52 plus or minus 2.77%, ATP 28.13 plus or minus 5.45%, and cAMP 26.01 plus or minus 3.34%. The absolute levels of adenine nucleotides in the secretory granules were ATP 4.19 plus or minus 0.88, ATP madp 7.94 plus or minus 2.20 and cAMP 4.46 plus or minus 1.74 pmol/ug prot. The levels in the islet effluent were ATP, 15.30 plus or minus 2.70, ATP qDP, 29.43 plus or minus 3.49 and cAMP 7.66 plus or minus 1.93 pmol/100 islets/min for the first ten min of glucose-stimulated insulin release. Thereafter there was a rapid decline in effluent cAMP while ATP and ADP remained in essentially equivalent amounts. The distribution of radioactivity and absolute levels of the adenine nucleotides in the effluent reflects that found in the secretory granules, confirming previous observations that insulin release is occurring by exocytosis.
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PMID:Adenine nucleotides in the secretory granule fraction of rat islets. 16 31

Hepatic gluconeogenesis in the rat does not begin until birth. The enzyme P-enolpyruvate carboxykinase appears initially at birth and is the final enzyme in the gluconeogenic sequence to develop. The appearance of this enzyme in the cytosol of rat liver is caused by the stimulation of enzyme synthesis, probably due directly to an increase in the hepatic concentration of cAMP. Enzyme degradation does not begin until 36 hours after birth. Studies with fetal rats in utero have shown that dibutyryl cAMP or glucagon will stimulate P-enolpyruvate carboxykinase synthesis and that this effect can be blocked by insulin. Insulin is known to depress the synthesis of P-enolpyruvate carboxykinase in adult rat liver and in Reuber H-35 liver cells in culture. The glucocorticoids are without effect on the synthesis of the enzyme in fetal rat liver. Work by Girard et al. (J. Clin. Invest. 52: 3190, 1973) has established that the molar ratio of insulin to glucagon drops from 10 immediately after birth, to 1 after one hour. This is due to both a rise in glucagon and a fall in insulin concentrations at birth. These studies, together with our work on the synthesis of P-enolpyruvate carboxykinase, indicate that the sharp drop in the concentration of insulin may relieve the normal inhibition of enzyme synthesis. This would allow the initial stimulation of enzyme synthesis by the glucagon-mediated rise in the concentration of CAMP.
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PMID:Hormonal regulation of hepatic P-enolpyruvate carboxykinase (GTP) during development. 16 70


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