PDX-1 INDUCES INSULIN AND GLUCOKINASE GENE EXPRESSIONS IN ALPHA-TC1 CLONE-6 CELLS IN THE PRESENCE OF BETACELLULIN

The pancreatic beta- and alpha-cells are developmentally related to ea ch other but reveal diverse gene expression patterns. Among the two im portant transcription factors for insulin gene expression, IEF1 is pre sent both in alpha- and beta-cells, but PDX-1/IPF1/STF-1/IDX-1, a home odomain-containing transcription factor, is present in beta-cells but not in alpha-cells. To elucidate the function of PDX-1 in the expressi on of beta-cell-specific genes, we established stable alpha TC1 clone 6 (alpha TC1.6)-derived transfectants expressing PDX-1 and examined th e changes in the gene expression patterns in them. The exogenous expre ssion of PDX-1 in alpha TC1.6 cells alone could induce islet amyloid p olypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene. However, when betacellulin was added to the medium, the PDX-1-expressing alpha TC1.6 cells, but not the control alpha TC1.6 cells, came to express insulin and glucokinase mRNAs. This did not occur with other growth factors such as epidermal growth factor, transforming growth factor a, and insulin-like growth factor I. GLUT2 mRNA remained undetectable in the PDX-1-expressing alp ha TC1.6 cells. These observations demonstrate the potency of PDX-1 fo r the expression of the insulin, glucokinase, and IAPP genes and sugge st that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene ex pression.