GLP-1 receptor signaling protects pancreatic beta cells in intraportal islet transplant by inhibiting apoptosis |
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Authors: | Toyoda Kentaro Okitsu Teru Yamane Shunsuke Uonaga Taeko Liu Xibao Harada Norio Uemoto Shinji Seino Yutaka Inagaki Nobuya |
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Institution: | a Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto 606-8507, Japan b Transplantation Unit, Kyoto University Hospital, Kyoto 606-8507, Japan c Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan d Kansai Denryoku Hospital, Osaka 553-0003, Japan e CREST of Japan Science and Technology Cooperation (JST), Kyoto, Japan |
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Abstract: | To clarify the cytoprotective effect of glucagon-like peptide-1 receptor (GLP-1R) signaling in conditions of glucose toxicity in vivo, we performed murine isogenic islet transplantation with and without exendin-4 treatment. When a suboptimal number of islets (150) were transplanted into streptozotocin-induced diabetic mice, exendin-4 treatment contributed to the restoration of normoglycemia. When 50 islets expressing enhanced green fluorescent protein (EGFP) were transplanted, exendin-4 treatment reversed loss of both the number and mass of islet grafts one and 3 days after transplantation. TUNEL staining revealed that exendin-4 treatment reduced the number of apoptotic beta cells during the early posttransplant phase, indicating that GLP-1R signaling exerts its cytoprotective effect on pancreatic beta cells by inhibiting their apoptosis. This beneficial effect might be used both to ameliorate type 2 diabetes and to improve engraftment rates in clinical islet transplantation. |
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Keywords: | Exendin-4 Glucagon-like peptide-1 Cytoprotection Apoptosis Enhanced green fluorescent protein Islet transplantation Islet engraftment |
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