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Inhibition of gluconeogenesis by hypoglycin in the rat. Evidence for inhibition of glucose-6-phosphatase in vivo.

Abstract
Treatment of rats with hypoglycaemic doses of hypoglycin has been shown to abolish the relative detritiation of [2-3H,U-14C]glucose [Osmundsen, Billington, Taylor & Sherratt (1978) Biochem. J. 170, 337-342], indicating that both the Cori and the glucose/glucose 6-phosphate cycles were inhibited in vivo. This inhibition was confirmed and, in addition, it was shown that the conversion in vivo of both [14C]lactate and [14C]fructose into glucose was decreased after hypoglycin treatment. These results suggest that hypoglycin poisoning results in the inhibition in vivo of glucose-6-phosphatase activity, which participates in the overall inhibition of gluconeogenesis and hypoglycaemia. Clofibrate feeding apparently protected the rats against the inhibition of the fructose-to-glucose conversion by hypoglycin. However, in isolated hepatocytes prepared from hypoglycin-treated rats, the conversion of [14C]fructose into glucose and the recycling of [2-3H,U-14C]glucose were not different from that in control hepatocytes. This suggests that the inhibition was lost during preparation of the hepatocytes. The direct measurement of glucose-6-phosphatase activity showed that it was inhibited when measured in concentrated, but not dilute, homogenates prepared from hypoglycin-treated rats.
AuthorsL Hue, H S Sherratt
JournalThe Biochemical journal (Biochem J) Vol. 240 Issue 3 Pg. 765-9 (Dec 15 1986) ISSN: 0264-6021 [Print] England
PMID3030285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cyclopropanes
  • Hypoglycins
  • hypoglycin
  • Phosphorylases
  • Glucokinase
  • Pyruvate Kinase
  • Protamine Kinase
  • Glucose-6-Phosphatase
Topics
  • Animals
  • Cyclopropanes (pharmacology)
  • Glucokinase (antagonists & inhibitors)
  • Gluconeogenesis (drug effects)
  • Glucose-6-Phosphatase (antagonists & inhibitors)
  • Hypoglycins (pharmacology)
  • In Vitro Techniques
  • Liver (cytology, enzymology, metabolism)
  • Male
  • Phosphorylases (antagonists & inhibitors)
  • Protamine Kinase (antagonists & inhibitors)
  • Pyruvate Kinase (antagonists & inhibitors)
  • Rats
  • Rats, Inbred Strains

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