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Exendin-4 Increases...
Exendin-4 Increases the Expression of Hypoxia-InducibleFactor-1 in Rat Islets and Preserves the Endocrine CellVolume of Both Free and Macroencapsulated Islet Grafts
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Jia, Xiaohui (författare)
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Sharma, Amit (författare)
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- Kumagai-Braesch, Makiko (författare)
- Karolinska Institutet
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- Wernerson, Annika (författare)
- Karolinska Institutet
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Sörenby, Anne (författare)
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- Yamamoto, Shinji (författare)
- Karolinska Institutet
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Wang, Feng (författare)
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Tibell, Annika (författare)
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(creator_code:org_t)
- 2012
- 2012
- Engelska.
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Ingår i: Cell Transplantation. - 0963-6897. ; 21:6, s. 1269-1283
- Relaterad länk:
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- In this study, we evaluated the effects of exendin-4 on free and encapsulated islet grafts in a rodent model.We also investigated the role of a transcription factor, hypoxia-inducible factor-1 (HIF-1), in mediating thebeneficial effects of exendin-4. Diabetic athymic mice were transplanted with free rat islets under the kidneycapsule or with macroencapsulated rat islets SC with or without exendin-4, islet preculture (exendin-4 0.1nM for 20 h), and/or recipient treatment (IP 100 ng/day, day 0–7). The mice were followed for 4 weeks andthe graft function andβ-cell volume were evaluated. The effects of exendin-4 on islet HIF-1α mRNAand protein expression and on ATP content in a rat insulinoma cell line (INS-1E) were also examined.Preculture with exendin-4 followed by recipient treatment improved the outcome of both free (73% graftfunction vs. 26% in controls,p = 0.03) and macroencapsulated islet grafts (100% vs. 25% in controls, p =0.02). In macroencapsulated grafts, the exendin-4-treated group had significantly larger endocrine volume,less graft necrosis, and more blood vessels around the capsule. In rat islets cultured with exendin-4, HIF-1αmRNA and protein expression were significantly enhanced. ATP content was increased in exendin-4-treatedINS-1E cells under hypoxic conditions. The improved functional outcome after transplantation of a marginalislet mass with a brief initial treatment with exendin-4 is related to a larger surviving endocrine cell volume.Exendin-4 may improve islet graft resistance to hypoxia during the peritransplant period by increasing theexpression of HIF-1
Nyckelord
- islet transplantation
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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