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Diabetes 52:1732-1737, 2003
© 2003 by the American Diabetes Association, Inc.

PDX-1 Protein Containing Its Own Antennapedia-Like Protein Transduction Domain Can Transduce Pancreatic Duct and Islet Cells

Hirofumi Noguchi, Hideaki Kaneto, Gordon C. Weir, and Susan Bonner-Weir

From the Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts

The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology.

Address correspondence and reprint requests to Dr. Susan Bonner-Weir, Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: susan.bonner-weir{at}joslin.harvard.edu


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