Development of regeneration therapy for type 1 diabetes by induction of β cell neogenesis

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Induction of β cell neogenesis which improve endogenous insulin secretory capacity in insulin-deficient type of diabetes will develop the new therapeutic strategy for diabetes as a regeneration therapy. In this research, we investigated the process of β cell neogenesis or differentiation in adult diabetic pancreas, and tried to develop the method for induction or acceleration of β cell neogenesis, thereby Individual glucose tolerance may be ameliorated by the increase of β cell mass.In the duct ligation model in which β cell neogenesis from ducts are frequently observed in the ligated portion, we detected several growth/differentiation factors such as IGF-1, TGF-β, betacellulin (BTC), HB-EGF that are known to be involved in the process of β cell growth and/or differentiation. In addition, we also detected induction of transcription factors including PDX-1, Pax6, Islet 1 and Nkx2.2, suggesting that they are closely associated with the process of β cell differentiation from duct cells or … More endocrine precursor cells in the duct lining.We also examined the in vivo effect of BTC and HB-EGF that belong to growth factor of EGF fatuity, and have been considered to be a possible β cell differentiation factor, using control and diabetic model mice-including NOD (non-obese diabetic) mice. Both BTC and HB-EGF showed a potency to induce β cell differentiation from duct cells and significantly increased newly formed Islet-like cell clusters (ICCs) , and significant improvement of glucose tolerance assessed by IPGTT (intra-peritoneal glucose tolerance test) in control mice. However, no significant improvement of glucose tolerance in diabetic mice induced by partial perfusion of alloxan and NOD mice were observed in spite of the appearance of ICCs, indicating that the increase of β cell mass induced by these factors was not enough to ameliorate glucose intolerance. Nevertheless, this approach to induce β cell neogenesis may provide a new regeneration therapy for type 1 and/or insulin-deficient type of diabetes mellitus. Less