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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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2012 (English)In: Cell Transplantation, ISSN 0963-6897, Vol. 21, 1269-1283 p.Article in journal (Refereed) Published
Abstract [en]

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 the

beneficial effects of exendin-4. Diabetic athymic mice were transplanted with free rat islets under the kidney

capsule or with macroencapsulated rat islets SC with or without exendin-4, islet preculture (exendin-4 0.1

nM for 20 h), and/or recipient treatment (IP 100 ng/day, day 0–7). The mice were followed for 4 weeks and

the graft function and

β-cell volume were evaluated. The effects of exendin-4 on islet HIF-1α mRNA

and 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% graft

function 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-1


mRNA and protein expression were significantly enhanced. ATP content was increased in exendin-4-treated

INS-1E cells under hypoxic conditions. The improved functional outcome after transplantation of a marginal

islet 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 the

expression of HIF-1


Place, publisher, year, edition, pages
2012. Vol. 21, 1269-1283 p.
Keyword [en]
islet transplantation
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-244842DOI: 10.3727/096368911X627408OAI: oai:DiVA.org:uu-244842DiVA: diva2:789981
Available from: 2015-02-22 Created: 2015-02-22 Last updated: 2015-02-22

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Publisher's full texthttp://dx.doi.org/10.3727/096368911X627408

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Yamamoto, Shinji
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