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)

Carbohydrate metabolism and vitamin-B6 status were assessed before and after pyridoxine administration in 46 women taking combined oestrogen-progestagen oral contraceptives (O.C.). 18 women had evidence of tissue depletion of vitamin B6, although all the women had abnormal tryptophan metabolism, including increased urinary xanthurenic acid (X.A.) excretion. In the women with vitamin B6 deficiency, administration of this vitamin caused elevation of fasting blood-pyruvate levels, and reduction in plasma glucose, insulin, and blood-pyruvate responses after an oral glucose load. These changes in carbohydrate metabolism were not found in the 28 non-vitamin-B6-deficient women. These results indicate that carbohydrate intolerance in women on O.C. is unlikely to be mediated by the formation of a complex of X.A. with insulin, as has formerly been proposed. Since the synthesis of the tryptophan metabolite quinolinic acid, an inhibitor of the heptaic enzyme phosphoenolpyruvate carboxykinase, may be enhanced by the administration of pyridoxine, it is suggested that this metabolite might be the important factor in the improvement of glucose tolerance in the vitamin-B6-deficient women. This conclusion is supported by the improvement in glucose tolerance observed in 6 women on O.C. and in 4 patients with glucocorticoid excess who were not vitamin-B6 deficient, when they were given tryptophan to augment the synthesis of quinolinic acid.
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PMID:Influence of oral contraceptives, pyridoxine (vitamin B6), and tryptophan on carbohydrate metabolism. 5 85

The activity of phosphoenolpyruvate carboxykinase (GTP) in Reuber H-35 cells was decreased after the removal of 6-N,2-O-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) from the medium. The decrease in activity was shown immunochemically to be the result of a rapid cessation in specific enzyme synthesis, occurring with a half-time of 40 min. The removal of dexamethasone, a less potent inducer of the enzyme in these cells, did not effect the activity of P-enolpyruvate carboxykinase or its rate of synthesis. Insulin added to either dibutyryl cyclic AMP or dexamethasone-treated cells produced a decline in specific enzyme synthesis which was not as rapid as that observed upon removal of dibutyryl cyclic AMP. This effect of insulin did not require the presence of glucose in the culture medium. Estimates of the half-life of the mRNA for P-enolpyruvate carboxykinase using actinomycin D and cordycepin suggested that after the inhibition of transcription of mRNA, enzyme synthesis continued for periods considerably longer than that observed after deinduction caused by removal of dibutyryl cyclic AMP. In addition, the synthesis of the enzyme could be restimulated by dibutyryl cyclic AMP in the absence of RNA synthesis. It was proposed that the deinduction of phosphoenolpyruvate carboxykinase in these cells is being regulated at the post-transcriptional or translational level.
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PMID:Deinduction of phosphoenolpyruvate carboxykinase (guanosine triphosphate) synthesis in Reuber H-35 cells. 16 66

Antiserum prepared against rat liver cytosolic phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) is shown to specifically precipitate the enzyme from Reuber H-35 cells. Synthesis of phosphoenolpyruvate carboxykinase, as measured immunochemically, is increased by dibutyryl cAMP and dexamethasone, the nucleotide maximally producing a sixfold and the glucocorticoid a threefold change in rate. Studies with actinomycin D, cordycepin, and cycloheximide suggest dibutyryl cAMP acts at a translational or post-transcriptional site. Insulin prevents the increase in synthesis of phosphoenolpyruvate carboxykinase produced by either dibutyryl cAMP or dexamethasone. This antagonism is concentration dependent and does not require the simultaneous presence of glucose, pointing to a direct effect of the hormone on liver enzyme induction. It is suggested that hepatic phosphoenolpyruvate carboxykinase activity is regulated predominantly by the antagonistic interaction of cAMP (glucagon) and insulin on enzyme synthesis.
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PMID:Effects of cyclic adenosine monophosphate, dexamethasone and insulin on phosphoenolpyruvate carboxykinase synthesis in Reuber H-35 hepatoma cells. 16 54

Administration of cadmium chloride (1.0 mg/kg s.c.) to rats, twice a day for 7 days, significantly stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase, markedly increased the concentration of hepatic cyclic adenosine monophosphate and circulating blood glucose and significantly reduced serum insulin levels. Furthermore, subacute exposure to cadmium induced glucose intolerance that was associated with a decreased pancreatic secretory activity as evidenced by lowered insulinogenic indices and marked inhibition of phentolamine-stimulated insulin release. In contrast to cadmium, administration of selenium dioxide (2 X 1.0 mg/kg/day s.c., 7 days) failed to alter significantly the activities of gluconeogenic enzymes, hepatic cyclic adenosine monophosphate, blood glucose or serum insulin levels, glucose tolerance or the pancreatic secretory activity. However, administration of selenium concurrently with cadmium completely prevented the cadmium-induced increases of hepatic gluconeogenic enzymes. Treatment with selenium ameliorated the cadmium-induced hyperglycemia, hypoinsulinemia, glucose intolerance and the suppression of pancreatic secretory activity, whereas it failed to alter significantly the cadmium-induced elevation of hepatic cyclic AMP levels. Data provide evidence suggesting that subacute exposure to cadmium alters several parameters of carbohydrate metabolism and suppresses pancreatic secretory activity and that administration of selenium alone is without any appreciable effect on the above parameters. However, administration of selenium concurrently with cadmium prevents, to varying degrees, several of the cadmium-induced metabolic and functional changes.
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PMID:Protective effect of selenium on certain hepatotoxic and pancreotoxic manifestations of subacute cadmium administration. 17 75

Cadmium, in addition to producing a variety of toxic manifestations, is known to accumulate in certain "target" organs which include liver and kidney where histological and functional damage becomes apparent. The daily intraperitoneal injection of cadmium chloride for 21 or 45 days stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphatase and glucose-6-phosphatase elevated blood glucose and urea, and lowered hepatic glycogen in rats. Whereas chronic Cd treatment failed to alter adenosine-3', 5'-monophosphate phosphodiesterase (PDE) activity, cyclic AMP (cAMY and the activity of basal and fluoride-stimulated forms of hepatic adenylate cyclase (AC) were markedly increased. However, the cAMP binding to hepatic protein kinase was decreased as was the kinase activity ration. An acute dose of Cd decreased hepatic glycogen content and increased blood glucose, serum urea, and hepatic cAMP. Chronic exposure to Cd induced adrenal hypertrophy and augmented adrenal norepinephrine and epinephrine as well as the activity of adrenal tyrosine hydroxylase. This treatment decreased prostatic and testicular weights of mature rats. Although cAMP as well as AC activity of the prostate gland were reduced, cAMP binding to the prostatic protein kinase was increased as was the activity of the cAMP-dependent form of the enzyme. Testicular AC and PDE activities, however, were stimulated, although cAMP remained unaffected. Whereas the activities of the cAMP-dependent and the independent forms of testicular protein kinase were significantly depressed, the binding of cAMP to protein kinase from testes of Cd-treated rats was not affected. In most cases, the observed metabolic alterations persisted up to 28 days on cessation of Cd administration. Subacute Cd treatment suppressed pancreatic function as evidenced by lowered serum immunoreactive insulin (IRI) in presence of hyperglycemia, as well as by partial inhibition of phentolamine-stimulated increases in serum IRI. Although chronic Cd treatment failed to alter the concentration of brain stem norepinephrine and cerebrocortical acetylcholine esterase activity, serotonin levels of brain stem were depressed and the concentration of striatal dopamine and cerebrocortical acetylcholine were significantly elevated when compared with the values seen in control nonexposed animals.
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PMID:Aspects of the biochemical toxicology of cadmium. 17 84

Reuber H35 cells were pulse-labeled with radioactive leucine and the influence of hormones, serum, and amino acids on protein degradation was investigated during a subsequent chase period. Radioactive, immunoprecipitable phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) had a half-life of 5 to 6 hours which was not influenced by either N6, O2-dibutyryl adenosine 3':5'-monophosphate, dexamethasone, or insulin. The rate of phosphoenolpyruvate carboxykinase degradation was the same under steady state conditions as during the approach to a new steady state following hormonal induction or deinduction of the enzyme. Therefore, hormonal regulation of enzyme activity in vivo is the result of changes in the rate of enzyme synthesis. The rate of proteolysis for total cell proteins was increased under nutritional step-down conditions produced by the removal of serum or amino acids, or both, from the medium. This effect was completely prevented by insulin. Cycloheximide and puromycin, but not actinomycin D or cordycepin, inhibited protein degradation under step-down conditions but did not further decrease the basal rate of proteolysis measured in the presence of either insulin or serum plus amino acids. There was a good correlation between changes in proteolysis produced by serum and amino acids and changes in the degradation rate of phosphoenolpyruvate carboxykinase. Also, inhibition of proteolysis with cycloheximide and puromycin was accompanied by a decrease in the degradation rate for enzyme antigen. It is suggested that nutritional step-down leads either to the synthesis or activation of a proteolytic system.
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PMID:Infulence of hormones and medium composition on the degradation of phosphoenolpyruvate carboxykinase (GTP) and total protein in Reuber H35 cells. 18 1

Neonatal hypoglycemia is of frequent occurrence in fasted newborn babies or animals but the origin of this hypoglycemia is not fully understood. Studies performed in newborn rats have shown that liver glycogenolysis and gluconeogenesis occur immediately after birth and that the increase in the activities of key regulatory enzymes (phosphorylase, glycogen synthetase and phosphoenolpyruvate carboxykinase) results probably from the rise of plasma glucagon and the fall of plasma insulin induced by the "stress" of birth. When the liver glycogen stores have been exhausted, i.e. between 6 and 16 hours after birth, a profound hypoglycemia develops in fasting newborn rats. The inability of hepatic gluconeogenesis to produce sufficient glucose to meet the energy requirement of the newborn tissues results from a lack of fat-derived (free fatty acids and ketone bodies) and gluconeogenic (lactate, amino acids) substrates. The stage of appearance and the mechanisms regulating gluconeogenesis in other species including human are discussed.
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PMID:[Energy metabolism in the perinatal period (author's transl)]. 18 42

The effects of chronic oral ingestion of lead in doses ranging from 20-80 ppm were compared with those seen after the subacute exposure of rats to a 10 mg/kg daily dose of the heavy metal for 7 days. Irrespective of the treatment regimen used, lead treatment significantly increased the activities of renal pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase. The observed enhancement of kidney gluconeogenic enzymes in chronically treated animals was associated with a stimulation of the adenylate cyclase-cyclic AMP system, a rise in blood blucose and urea as well as a depression in hepatic glycogen and serum immunoreactive insulin (IRI) levels. In contrast, subacute exposure to lead failed to significantly alter cyclic AMP metabolism and the concentrations of liver glycogen, blood glucose, serum urea or IRI. Whwereas the insulinogenic index (the ratio of serum IRI to blood glucose concentration) was markedly suppressed in chronically treated rats, this ratio remained within normal limits following subacute exposure to the heavy metal. However, a marked decrease in the insulinogenic index was observed in subacutely treated rats 15 min after the administration of a glucose load. The data provide evidence to show that increased glucose synthesis as well as suppressed pancreatic function may be responsible for lead-induced disturbances in glucose homeostasis.
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PMID:Effects of subsacute and chronic lead treatment on glucose homeostasis and renal cyclic AMP metabolism in rats. 18 14

1. The development of glycerolkinase before and after birth was investigated in liver and kidney of rat and hamster. In rat liver, enzyme activity increased very slowly before birth and rapidly thereafter, reaching adult values at the 6th day of postnatal life. In hamster liver, glycerolkinase was considerably elevated already in utero, increased dramatically within the 1st day of postnatal life and reached adult values at the end of the 1st week. The development of hepatic glycerolkinase was compared with that of hepatic phosphoenolpyruvate carboxykinase of rat and hamster up to the 20th day of postnatal life. The different time-courses of the levels of these two enzymes before and after birth as well as the known kinetics of serum insulin, glucagon and corticosterone during that time suggested that none of these hormones is involved in the perinatal development of hepatic glycerolkinase activity. In contrast to liver, kidney glycerolkinase activity in both, rat and hamster, showed a delayed increase during the first week of postnatal life followed by a more pronounced elevation to adult values within the following 2 weeks. 2. When liver and kidney glycerolkinase activity was investigated during starvation (+/- refeeding), in alloxan diabetes(+/- insulin) and after adrenalectomy (+/- cortisol) no significant change in enzyme activity per g tissue could be detected either in liver or in kidney. However, total hepatic glycerolkinase activity was diminished during starvation as a consequence of decreasing liver weight. 3. Incorporation of U-[14C]-glycerol into CO2, lipids and glucose + glycogen by rat liver and kidney cortex slices was studied under the above gluconeogenetic conditions. Despite unchanged glycerolkinase activity in both organs, gluconeogenesis from glycerol was enhanced during starvation and in chronic alloxan diabetes, and could be reversed by refeeding and insulin replacement, respectively. 4. Feeding 20% of linolic acid to normal, alloxan-diabetic or adrenalectomized rats resulted in a significant increase in glycerolkinase activity in liver but not in kidney. 5. From the present findings it is suggested that the first step of gluconeogenesis from glycerol in liver and kidney is not influenced by glucagon, insulin and glucocorticoids, which are generally believed to regulate the rate of gluconeogenesis from non-glycerol precursors, but probably by the change in blood glycerol concentration.
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PMID:Glycerolkinase--a regulatory enzyme of gluconeogenesis? 18 91

The effect of re-feeding glucose, protein or fat and the effect of insulin injection on the activity of hepatic phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating) EC 4.1.1.32), the concentration of hepatic cyclic AMP and the level of serum insulin was investigated in starved rats. Under all conditions examined the concentration of serum insulin was elevated to a high degree. However, only rats re-fed with glucose responded to the increase in serum insulin with a decrease in PEP carboxykinase activity, while the activity of the enzyme remained unchanged or was elevated after re-feeding protein or fat or after insulin injection, respectively. Since under all conditions there was a close correlation between cyclic AMP concentration and PEP carboxykinase activity, but not between the insulin level and enzyme activity, it is concluded that the hormone physiologically regulates PEP carboxykinase activity by decreasing the intrahepatic cyclic AMP concentration rather than by the postulated cyclic AMP-independent inhibition of specific mRNA translation.
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PMID:Physiological regulation of rat liver phosphoenolpyruvate carboxykinase (GTP) by insulin. Insignificance of a cyclic AMP-independent mechanism. 19 43


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