H. Watada et al., PDX-1 INDUCES INSULIN AND GLUCOKINASE GENE EXPRESSIONS IN ALPHA-TC1 CLONE-6 CELLS IN THE PRESENCE OF BETACELLULIN, Diabetes, 45(12), 1996, pp. 1826-1831
Citations number
37
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
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.