REGULATIONS OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE AND LIPOGENESIS
Nakamura, Toshikazu The University of Tokushima
Yoshimoto, Katsuhiko The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Aoyama, Kazushi The University of Tokushima
Ichihara, Akira The University of Tokushima
In primary cultured monolayer hepatocytes of adult rats, insulin (1×10-8M) induced glucose-6-phosphate dehydrogenase [EC 184.108.40.206, G6PDH] several fold in 48h. It also induced lipogenesis, measured as [1-14C] acetate incorporation in 2h, in these cells. Of the various lipids, triglycerides and phospholipids were induced markedly, while cholesterol and its esters were not induced. The increase of G6PDH and lipogenesis were parallel. Glucagon, dibutyryl cyclic AMP, triiodothyronine, dexamethasone, epinephrine, isoproterenol, and dibutyryl cyclic GMP were also tested under similar conditions, but none of them caused significant induction of G6PDH or lipogenesis.
Use of anti-G6PDH serum showed that induction of G6PDH by insulin was due to increase in the amount of enzyme protein. Insulin was found to increase the rate of synthesis of G6PDH about 3-fold. SDS-polyacrylamide gel electrophoresis of the immunoprecipitable protein revealed that besides G6PDH another radioactive fraction (Mr 37,000) was increased by insulin. This suggests that complete synthesis of G6PDH protein is slowed down in primary cultured hepatocytes and that an apparent nascent peptide of the enzyme accumulates.
Although on long-term treatment (48h), glucagon and dibutyryl cyclic AMP had no effect on lipogenesis, when added with [14C] acetate for 2h they strongly inhibited lipogenesis. Significant inhibition of lipogenesis by short-term treatment with glucagon was seen even in cells with a high capacity for lipogenesis induced by long-term treatment with insulin. Insulin again stimulated lipogenesis in short-term treatment, but its effect was slight.
It is concluded from these results that insulin exerts long-term stimulation of lipogenesis by inducing enzymes related to lipogenesis including G6PDH as well as causing slight stimulation by enhancing supply of substrate for lipogenesis. Glucagon seems to play a minor role in long-term control, but it causes short-term inhibition of lipogenesis.
The Journal of Biochemistry
The Japanese Biochemical Society
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