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

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 16.7 mM 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.