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

Biochem Biophys Res Commun. 2007 Feb 16;353(3):617-22. doi: 10.1016/j.bbrc.2006.12.065. Epub 2006 Dec 19.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Enzyme Repression
  • Epithelial Cells / enzymology
  • Gene Expression Regulation, Enzymologic
  • Glucose / pharmacology*
  • Hepatocyte Nuclear Factor 1-alpha / biosynthesis
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-alpha / physiology*
  • Hepatocyte Nuclear Factor 1-beta / biosynthesis
  • Hepatocyte Nuclear Factor 1-beta / genetics
  • Hepatocyte Nuclear Factor 1-beta / physiology*
  • Humans
  • Mutation
  • Sucrase-Isomaltase Complex / biosynthesis*
  • Sucrase-Isomaltase Complex / genetics
  • Transfection

Substances

  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Sucrase-Isomaltase Complex
  • Glucose