HNF-1α participates in glucose regulation of sucrase–isomaltase gene expression in epithelial intestinal cells

Abstract: Sucrase–isomaltase (SI) gene expression is negatively regulated by glucose, but its molecular mechanism is not completely clear. The purpose of this study is to investigate whether HNF-1α and HNF-1β contribute to glucose regulation of SI gene expression. To explore this question, we examined the association of gene expressions between SI and HNF-1α and HNF-1β in Caco-2 cells cultured in medium containing 2.0 and 16.7mM glucose. We found that gene expression of HNF-1α but not HNF-1β exhibits a positive correlation with that of SI regulated by glucose. Moreover, to elucidate whether glucose regulation of SI gene expression is changed when HNF-1α and HNF-1β are inhibited, we produced three stable cell lines, in which dominant-negative mutant HNF-1αT539fsdelC, mutant HNF-1βR177X, and empty vector (as a control), respectively, were stably expressed. We found that the glucose regulation of SI gene expression was significantly attenuated in HNF-1αT539fsdelC cells, but it was well maintained in empty vector and HNF-1βR177X cells. These results suggest that HNF-1α participates in glucose regulation of SI gene expression. [Copyright &y& Elsevier]