%0 Journal Article
%T Regeneration of Pancreatic Non-¦Â Endocrine Cells in Adult Mice following a Single Diabetes-Inducing Dose of Streptozotocin
%A Yanqing Zhang
%A Yuan Zhang
%A Robert N. Bone
%A Wanxing Cui
%A Ji-Bin Peng
%A Gene P. Siegal
%A Hongjun Wang
%A Hongju Wu
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0036675
%X The non-¦Â endocrine cells in pancreatic islets play an essential counterpart and regulatory role to the insulin-producing ¦Â-cells in the regulation of blood-glucose homeostasis. While significant progress has been made towards the understanding of ¦Â-cell regeneration in adults, very little is known about the regeneration of the non-¦Â endocrine cells such as glucagon-producing ¦Á-cells and somatostatin producing ¦Ä-cells. Previous studies have noted the increase of ¦Á-cell composition in diabetes patients and in animal models. It is thus our hypothesis that non-¦Â-cells such as ¦Á-cells and ¦Ä-cells in adults can regenerate, and that the regeneration accelerates in diabetic conditions. To test this hypothesis, we examined islet cell composition in a streptozotocin (STZ)-induced diabetes mouse model in detail. Our data showed the number of ¦Á-cells in each islet increased following STZ-mediated ¦Â-cell destruction, peaked at Day 6, which was about 3 times that of normal islets. In addition, we found ¦Ä-cell numbers doubled by Day 6 following STZ treatment. These data suggest ¦Á- and ¦Ä-cell regeneration occurred rapidly following a single diabetes-inducing dose of STZ in mice. Using in vivo BrdU labeling techniques, we demonstrated ¦Á- and ¦Ä-cell regeneration involved cell proliferation. Co-staining of the islets with the proliferating cell marker Ki67 showed ¦Á- and ¦Ä-cells could replicate, suggesting self-duplication played a role in their regeneration. Furthermore, Pdx1+/Insulin£¿ cells were detected following STZ treatment, indicating the involvement of endocrine progenitor cells in the regeneration of these non-¦Â cells. This is further confirmed by the detection of Pdx1+/glucagon+ cells and Pdx1+/somatostatin+ cells following STZ treatment. Taken together, our study demonstrated adult ¦Á- and ¦Ä-cells could regenerate, and both self-duplication and regeneration from endocrine precursor cells were involved in their regeneration.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0036675