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Functional Dissimilarity with Several Other Glucose Response Elements
a Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, 1070 Brussels, Belgium
Key Words: gene promotor • glucagon receptor gene • glucose activation • fatty acids activation • pentose phosphate
Address for correspondence: M. Svoboda, Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, CP 611, Route de Lennik 808, B-1070 Brussels, Belgium. Voice: 32-2-555-62-25; fax: 32-2-555-62-30. e-mail: msvobod{at}ulb.ac.be
The glucagon receptor (GLR) expression is positively regulated by glucose. This regulation is allowed by the presence, in the promotor of the rat GLR gene, of a sequence feature similar to the two E-boxes motifs constituting the carbohydrate response elements (ChoRE) described for several glycolytic and lipogenic enzyme genes. Using reporter gene assays, we demonstrated here that, despite structural homologies with these ChoREs, the GLR gene glucose response element presents various functional dissimilarities.Testing glucose analogs, we demonstrated that, as for other genes, the glucose must be first phosphorylated. However, at variance with others homologue genes, our data showed the implication of the nonoxidative branch of the pentose phosphate pathway in the transmission of the glucose signal and lack of inhibition by adenosine monophosphate (AMP)-kinase. Furthermore, the activity of our reporter gene was strongly stimulated by butyrate, propionate, and acetate. This observation contrasts with fatty-acid-induced inhibition of the glucose activation, observed for all other genes containing homolog ChoREs. We also showed that glucose and butyrate influence the reporter gene expression via different features.
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