| Co-Investigator(Kenkyū-buntansha) |
KAJIMOTO Yoshitaka Osaka Univ., 1st Dept of Med., Fellow, 医学部・附属病院, 医員
YAMASAKI Yoshimitsu Osaka Univ., 1st Dept of Med., Assistant Prof., 医学部, 助手 (40201834)
MOCHIZUKI Kentaro Juntendo Univ., Dept of Med., Assistant Prof., 医学部, 助手 (40266044)
ARISAKA Tomoyuki Juntendo Univ., Dept of Med., Assistant Prof., 医学部, 助手 (30266043)
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| Research Abstract |
Because the future gene therapy for diabetes would require the use of the non-pancreatic beta-cells (such as myocyte-derived cells) which express insulin in the glucose-dependent manner, we investigated whether the exogenous expression of a transcription factor PDX-1 in non-beta-cells could induce the beta-cell-specific gene expressions. As an initial step, we established alphaTC1 clone 6(alphaTC1.6)-derived stable transfectants expressing PDX-1 and examined the changes in the gene expression patterns in them. The exogenous expression of PDX-1 in alphaTC1.6 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 betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells but not the control alphaTC1.6 cells came to express insulin and glucokinase mRNAs. This did not occur with other growth factors such as epidermal growth factor (EGF), transforming growth factor alpha(TGFalpha) and IGF-l, GLUT2 mRNA remained undetectable in the PDX-1-expressing alphaTC1.6 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 betacellulin, also contribute to the beta-cell specificity of gene expression. Thus our present study provides support for the potential usefulness of both PDX-1 and betacellulin for the conversion of non-beta-cells to beta-cell-like cells.
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