Molecular mechanisms controlling pancreatic β cell regeneration and pathophysiological significance of pancreatic nestin-expressing cells

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(Purpose) Pancreatic β cell is derived from endoderm. Similarities have been pointed out between pancreatic β cells and neuronal cells. In the present study, we investigated the significance of neurogenin 3 (ngn3), nestin, and notch2.(Methods and Results) NGN3 gene expression was very low in streptozotocin-induced pancreatic β cell regeneration rat model, indicating that ngn3 gene expression is not changed in β cell regeneration. Although ngn3 gene expression was noted in central nervous system of rat embryo, postnatally it was not detected in normal rats and in streptozotocin-induced pancreatic β cell regeneration rat model. Using GFP immunofluorescence and anti-GFP antibody, nestin was expressed in vascular endothelial cells of pancreata of streptozotocin-induced pancreatic β cell regeneration rat model and normal rats. Postnatally, using Notch2-LacZ knock-in mouse and immunohistochemistry of anti-Notch2 antibodies, notch2 is expressed mainly in pancreatic duct cells.(Discussion) Since ngn3 was not detected in postnatal pancreas, the significance of ngn 3 in postnatal pancreatic regeration remains to be elucidated. In the present study, nestin was demonstrated to be expressed in vascular endothelial cells. Since β cell is derived from endodermal origin, nestin-expressing cells appear to be precursors of pancreatic β cells. Pancreatic duct cells has been proposed to be derived from pancreatic duct cells. Notch2-expressing cells may be precursors of β cells. We are investing the significance of notch2 using pancreas-tissue specifc kock-out mice.