Impairment of Glucokinase Translocation in Cultured Hepatocytes from OLETF and GK Rats, Animal Models of Type 2 Diabetes.

  • TOYODA Yukiyasu
    Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University
  • ITO Yuki
    Pharmacy of Nagoya Daini Red Cross Hospital
  • TANIGAWA Keiichiro
    Department of Clinical Nutrition, Faculty of Health Science, Suzuka University of Medical Science
  • MIWA Ichitomo
    Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University

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We examined sugar-induced translocation of glucokinase in cultured hepatocytes from Otsuka Long-Evans Tokushima Fatty and Goto-Kakizaki rats, animal models of type 2 diabetes, and compared this with that in Long-Evans Tokushima Otsuka and Wistar rats, respectively, as control strains. When hepatocytes from the four strains were incubated with 5 mM glucose, glucokinase was present predominantly in the nuclei. Higher concentrations of glucose, 5 mM glucose plus 1 mM fructose, and 5 mM glucose plus 1 mM sorbitol all induced the translocation of glucokinase from the nucleus to the cytoplasm in hepatocytes from these rats. The extent of glucokinase translocation under these conditions, however, was less marked in both diabetic rat types than in the control rats. The extent of the phosphorylation of glucose as estimated by the release of 3H2O from [2-3H] glucose is significantly lower in Goto-Kakizaki rats than in Wistar rats. The results indicate that the translocation of glucokinase is impaired in the hepatocytes of diabetic rats. They also suggest that the impaired translocation of glucokinase is associated with abnormal hepatic glucose metabolism in type 2 diabetes.

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