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Diet Differentially Regulates Glucokinase and L-type Pyruvate Kinase Gene Expression in Rat Liver^1,2,

Tezukayama Gakuin College, Sakai, Osaka 590-01 ^* Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Suita, Osaka 565, Japan

The regulation of gene expression of glucokinase (GK) and L-type pyruvate kinase (L-PK) in rat liver was investigated and compared with the previously reported regulation of lipogenic enzymes. Experiments were conducted in which the time courses and responses to diet quantity of mRNA concentrations and enzyme activities after refeeding a carbohydrate/protein diet (CP) to food-deprived rats were measured. The effects of dietary nutrients on the gene expression were investigated in rats refed either the CP diet, a carbohydrate diet without protein (C), a protein diet without carbohydrate (P), or a carbohydrate/protein/corn oil diet (CPF). The effects of the CPF diet on the gene expression after insulin treatment to diabetic rats were also investigated. After refeeding the CP diet, GK mRNA concentration and enzyme activity reached maximum levels in 2 h and 16–24 h, respectively, whereas those of L-PK peaked in 16 h and 48 h, respectively, similar timecourse to lipogenic enzymes. Moreover, GK mRNA concentrations were maximal in rats fed 20% of the ad libitum diet intake, and L-PK mRNA concentrations, like lipogenic enzyme mRNA, were maximal in rats fed 50% of ad libitum intake. GK mRNA concentrations were significantly increased in parallel with an increase in plasma insulin and glucose concentrations. GK and L-PK mRNA and enzyme levels in rats fed the C diet were comparably induced to the levels in those fed the CP diet. L-PK mRNA induction by the CP diet was significantly reduced by dietary polyunsaturated fatty acids (CDF diet), whereas the GK mRNA induction was not significantly reduced. However, both L-PK and GK mRNA induction by insulin treatment of diabetic rats was significantly reduced by dietary polyunsaturated fatty acids (CPF). Thus, L-PK gene expression, similar to lipogenic enzyme gene expression was regulated by dietary nutrients, but GK gene expression was more rapidly regulated by a lesser quantity of dietary carbohydrate.

KEY WORDS: • glycolytic enzymes • gene expression • nutrients • rats

¹ Supported by a grant from Tezukayama Gakuin College and partially supported by Japan Private School promotion funds.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 7 April 1995. Revision accepted 7 August 1995.