HNF-1alpha 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-1alpha and HNF-1beta contribute to glucose regulation of SI gene expression. To explore this question, we examined the association of gene expressions between SI and HNF-1alpha and HNF-1beta in Caco-2 cells cultured in medium containing 2.0 and 16.7 mM glucose. We found that gene expression of HNF-1alpha but not HNF-1beta 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-1alpha and HNF-1beta are inhibited, we produced three stable cell lines, in which dominant-negative mutant HNF-1alphaT539fsdelC, mutant HNF-1betaR177X, 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-1alphaT539fsdelC cells, but it was well maintained in empty vector and HNF-1betaR177X cells. These results suggest that HNF-1alpha participates in glucose regulation of SI gene expression.
Gu
Ning
N
Laboratory of Metabolism, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.
Adachi
Tetsuya
T
Matsunaga
Tetsuro
T
Tsujimoto
Gozoh
G
Ishihara
Akihiko
A
Yasuda
Koichiro
K
Tsuda
Kinsuke
K
D018938:Caco-2 Cells; D004794:Enzyme Repression; D004847:Epithelial Cells / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000494:pharmacology*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051539:Hepatocyte Nuclear Factor 1-beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009154:Mutation; D013394:Sucrase-Isomaltase Complex / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D013394:Sucrase-Isomaltase Complex; D005947:Glucose