Inhibition of gluconeogenesis by hypoglycin: Alternate interpretations

• Published in: Hepatology (Baltimore, Md.) Md.), 1987-11, Vol.7 (6), p.1377-1379
• Main Author: Tanaka, Kay
• Format: Article
• Language: English
• Subjects: Animals; Cyclopropanes - pharmacology; Fatty Acid Desaturases - antagonists & inhibitors; Gluconeogenesis - drug effects; Glucose-6-Phosphatase - antagonists & inhibitors; Humans; Hypoglycemia - chemically induced; Hypoglycins - pharmacology; Liver - cytology; Liver - enzymology; Liver - metabolism; Plant Poisoning - etiology; Plant Poisoning - metabolism; Rats
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.1840070633

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, W‐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.