Mechanism of differentiation and growth of pancreatic βcells by newly identified growth factor, NTAK, and its application for regenerative medicine in diabetes mellitus

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We have been studied on the mechanism of regeneration and differentiation, and apoptosis of pancreatic β cells to develop the new therapeutic approach to diabetes mellitus. In this research, we investigated the possible involvement of neural-and thymus-derived activator for ErbB kinases (NTAK), newly identified growth factor which belongs to the EGF family, and CD 9, one of the modulators of EGF family signal transduction. We demonstrated the adult and fetal pancreas produced NTAK which is localized in β cells and fetal pancreatic epithelial cells including endocrine precursor cells, respectively. CD-9 also expressed on islet cells. These results suggested that NTAK and CD-9 may be involved in the mechanism of differentiation and/or proliferation of pancreatic β cells in addition to the development of pancreas.In vitro peptide study of NTAK revealed that partial sequence of peptides of NTAK showed the activity of proliferation, while some other part of peptide sequence inhibited the proliferation of β cell line, MIN6 cells, suggesting that NTAK signal transduction may be involved in both positive and negative (apoptotic?) regulatory pathways for β cell proliferation and/or differentiation. Further study is necessary to elucidate the detailed signal transduction pathway(s) of NTAK in pancreatic β cells.