Inhibition of gluconeogenesis by hypoglycin in the rat. Evidence for inhibition of glucose-6-phosphatase in vivo.
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.
D000818:Animals; D003521:Cyclopropanes / Q000494:pharmacology*; D005941:Glucokinase / Q000037:antagonists & inhibitors; D005943:Gluconeogenesis / Q000187:drug effects*; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors*; D007005:Hypoglycins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D006005:Phosphorylases / Q000037:antagonists & inhibitors; D006656:Protamine Kinase / Q000037:antagonists & inhibitors; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains
D003521:Cyclopropanes; D007005:Hypoglycins; C041757:hypoglycin; D006005:Phosphorylases; D005941:Glucokinase; D011770:Pyruvate Kinase; D006656:Protamine Kinase; D005952:Glucose-6-Phosphatase