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Glucose‐dependent regulation of the l ‐pyruvate kinase gene in a hepatoma cell line is independent of insulin and cyclic AMP
Author(s) -
LefrançoisMartinez Anne Marie,
DiazGuerra MariaJose M.,
Vallet Véronique,
Kahn Axel,
Antoine Bénédicte
Publication year - 1994
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.8.1.8299894
Subject(s) - glucokinase , hepatocyte , insulin , biology , pyruvate kinase , insulin receptor , medicine , glycolysis , endocrinology , cell culture , insulin receptor substrate , chemistry , microbiology and biotechnology , biochemistry , metabolism , insulin resistance , in vitro , genetics
Hepatocyte‐like mhAT3F cells have been derived from the hepatoma of a transgenic mouse expressing the SV40 large T antigen under the control of the antithrombin III gene regulatory region (Antoine, B., Levrat, F., Vallet, V., Berbar, T., Cartier, N., Dubois, N., Briand, P., and Kahn, A. (1992) Gene expression in hepatocyte‐like lines established by targeted carcinogenesis in transgenic mice. Exp. Cell. Res. 200, 175–185; F. Levrat et al., unpublished results). In these cells, the l ‐PK gene is transcriptionally activated by glucose, as it is in vivo and in cultured hepatocytes. However, in contrast to the l ‐PK gene regulation in the liver and isolated hepatocytes, the glucose responsiveness does not require insulin and is not blocked by cyclic AMP. In mhAT3F cells, the insensitivity to insulin might be due to the replacement of insulin‐dependent glucokinase by insulin‐independent hexokinases able to phosphorylate glucose in the absence of the hormone. The glucose‐dependent activation of the l ‐PK gene is delayed, requires ongoing protein synthesis, and is mediated by the same glucose response element as in vivo and in isolated hepatocytes. These results suggest that the glucose‐dependent signaling pathway responsible for the transcriptional activation of glycolytic and lipogenic genes requires glucose phosphorylation, a phenomenon that is insulin‐dependent in the liver but insulin‐independent in cultured hepatoma cells. Nevertheless, the action of glucose 6‐phosphate is most likely indirect.— Lefrançois‐Martinez, A.‐M., Diaz‐Guerra, M.‐J. M., Vallet, V., Kahn, A., Antoine, B. Glucose‐dependent regulation of the L‐pyruvate kinase gene in a hepatoma cell line is independent of insulin and cyclic AMP. FASEB J. 8: 89‐96; 1994.