Abstract
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ISLET BIOLOGY AND TRANSPLANTATION J-H JUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Taiwan
The pancreatic islets of Langerhans have been intensively investigated, largely because of their central role in the pathogenesis of type 1 and type 2 diabetes mellitus. Research studies centered on WKH ELRORJ\ UHJHQHUDWLRQ DQG WUDQVSODQWDWLRQ RI LVOHWV FRQWLQXH WR VKHG VLJQL¿FDQW XQGHUVWDQGLQJ RQ the development of different forms of diabetes and provide further impetus for the quest to find a “cure.” Restoring E-cell mass and reversing diabetes can be accomplished by two approaches: either by endogenous regeneration of E cells or transplantation of E cells from exogenous sources; recent advancements in science and technology have facilitated progress in both. The following are examples RI RXU UHVHDUFK ZRUN LQ WKLV ¿HOG It has been shown all-trans retinoid acid (ATRA) hinders the development of autoimmune diabetes by inducing immune tolerance status. Meanwhile, exendin-4 stimulates growth and differentiation of E cells as well as exerts antiapoptotic effect on E cells. Thus, we tested if the combination therapy with ATRA and exendin-4 could prevent and rescue diabetes in NOD mice with and without islet transplantation. We found ATRA and ATRA plus exendin-4 treatment delayed the onset of diabetes. However, after the onset of autoimmune diabetes, ATRA and/or exendin-4 treatment is unable to reverse hyperglycemia or improve survival in NOD mice with and without islet transplantation. To better understand the fate of islet isografts and allografts, we utilized a magnetic resonance (MR) imaging technique to monitor mouse islets labeled with a novel MR contrast agent, chitosancoated superparamagnetic iron oxide (CSPIO) nanoparticles. After incubation of mouse islets with CSPIO, TEM showed CSPIO in endocytotic vesicles of D and E cells at 8 h. Incubation with CSPIO did not affect insulin secretion and death rates of islets. After syngeneic and allogeneic transplantation, grafts of CSPIO-labeled islets were visualized on MR scans as persistent hypointense areas. At 8 weeks after syngeneic transplantation and 31 days after allogeneic transplantation, histology of CSPIO-labeled islet grafts showed colocalized insulin and iron staining in the same areas but the size of allografts decreased with time. TEM with elementary iron mapping demonstrated CSPIO distributed in the cytoplasm of islet cells, which maintained intact ultrastructure.
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