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)

Asparagine stimulated the translation of ornithine decarboxylase (ODC) mRNA more than 10-fold in cultured hepatocytes which had been pretreated with glucagon in simple salt/glucose medium. Putrescine suppressed the increase in the rate of ODC synthesis caused by asparagine without significant change in the amount of ODC mRNA, suggesting that putrescine inhibited the effect of asparagine at least in part at the level of translation. Polysomal distribution of ODC mRNA was analyzed to examine the site of translational regulation by these effectors. In uninduced hepatocytes, most of the ODC mRNA was sedimented slightly after the 40 S ribosomal subunit. This ODC mRNA was sequestered from translational machinery since it was not shifted to the polysome fraction when peptide elongation was specifically inhibited by a low concentration of cycloheximide. In asparagine-treated cells, 40% of total ODC mRNA was in the polysomal fraction and formed heavier polysomes, indicating that asparagine stimulated both recruitment of ODC mRNA from the untranslatable pool and the initiation steps of translation. Putrescine did not change the distribution pattern of ODC mRNA on polysomes significantly. Thus, 30% of ODC mRNA remained on polysomes even when ODC synthesis was completely inhibited by putrescine. Paradoxically more than 70% of ODC mRNA was shifted into polysomes by putrescine in the presence of low concentrations of cycloheximide. These results, together with changes in the polysome profile, suggested that putrescine nonspecifically stimulated the recruitment of ODC mRNA from the untranslatable pool, whereas it specifically inhibited its translation at both the initiation and the elongation steps.
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PMID:Translational control mechanism of ornithine decarboxylase by asparagine and putrescine in primary cultured hepatocytes. 195 37

When insulin and glucagon are administered to rats with severe liver injury, survival is enhanced with an attenuation of the liver injury compared to that of untreated controls. In rats with acute liver injury both hormones produce a rapid normalization of hepatic protein content following initiation of DNA synthesis. When rats receive both hormones after partial hepatectomy, the first burst of DNA synthesis reaches a maximum earlier than that seen in controls. Both hormones enhance the increment of hepatic putrescine essential for DNA synthesis through activation of ornithine decaroxylase and/or spermidine-N1-acetyltransferase. The enhancement of putrescine content by each hormone is additive. Putrescine supplementation promotes hepatic DNA synthesis after hepatectomy. Based on these data, we conclude that a combination of insulin and glucagon is effective in the therapy of acute hepatic failure in rats. The restoration of liver function as well as the stimulation of liver cell proliferation via putrescine production may contribute to this effect.
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PMID:Insulin and glucagon therapy of acute hepatic failure. 203 21

We studied the effect of putrescine on acute liver failure caused in rats by two injections of 1 gm/kg D-galactosamine. The hepatic polyamine level rose only slightly in the D-galactosamine-injected rats treated with glucagon and insulin, and [3H]thymidine incorporation into DNA increased little; these hormones did not improve the survival rate. When D-galactosamine-injected rats were given putrescine, the putrescine concentration in the liver increased and the survival rate of the rats was significantly higher than that of control rats given only D-galactosamine. Putrescine administration tended to lower the serum level of alanine aminotransferase in rats injected with D-galactosamine, so the polyamine might have a protective effect on hepatocytes. Putrescine significantly increased [3H]thymidine incorporation in the liver; thus it accelerated liver regeneration. Difluoromethylornithine decreased the level of putrescine in the liver, decreasing both [3H]thymidine uptake and the survival rate. In the rats treated with D-galactosamine, in which liver damage was so severe that treatment with glucagon and insulin was ineffective, the intraperitoneal administration of putrescine increased the survival rate in acute liver failure. This probably resulted mainly from activation of liver regeneration and possibly from a protective effect of putrescine on the liver.
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PMID:Effects of putrescine on D-galactosamine-induced acute liver failure in rats. 239 Oct 73

When rats received glucagon or insulin every 2 h after partial hepatectomy (Hx), hepatic putrescine content was increased above control levels at 6 and 12 h, respectively. When the two hormones were combined, the increased levels were additive. Hepatic ornithine decarboxylase activity was above control levels at 12 h after insulin treatment. Hepatic spermidine N1-acetyltransferase activity was enhanced at 6 h only when glucagon was dosed. Putrescine administration from 0 to 4 h or from 6 to 10 h increased hepatic DNA synthesis to similar levels 22 h after Hx. These results suggest that glucagon and insulin additively stimulate hepatic putrescine production after Hx. This may explain the cooperative stimulation of liver regeneration by both hormones.
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PMID:Additive stimulation of hepatic putrescine production by glucagon and insulin after partial hepatectomy in rats. 266 92