PDX-1 Induces Insulin and Glucokinase Gene Expressions in αTC1 Clone 6 Cells in the Presence of Betacellulin

Abstract

The pancreatic β- and α-cells are developmentally related to each other but reveal diverse gene expression patterns. Among the two important transcription factors for insulin gene expression, IEF1 is present both in α- and β-cells, but PDX-1/IPF1/STF-1/IDX-1, a homeodomain-containing transcription factor, is present in β-cells but not in α-cells. To elucidate the function of PDX-1 in the expression of β-cell-specific genes, we established stable αTC1 clone 6 (αTC1.6)-derived transfectants expressing PDX-1 and examined the changes in the gene expression patterns in them. The exogenous expression of PDX-1 in αTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene. However, when βcellulin was added to the medium, the PDX-1-expressing αTC1.6 cells, but not the control αTC1.6 cells, came to express insulin and glucokinase mRNAs. This did not occur with other growth factors such as epidermal growth factor, transforming growth factor α, and insulin-like growth factor I. GLUT2 mRNA remained undetectable in the PDX-1–expressing αTC1.6 cells. These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by βcellulin, also contribute to the β-cell specificity of gene expression.