PMID- 22405036
OWN - NLM
STAT- MEDLINE
DCOM- 20130501
LR  - 20181202
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 21
IP  - 6
DP  - 2012
TI  - Exendin-4 increases the expression of hypoxia-inducible factor-1alpha in rat islets 
      and preserves the endocrine cell volume of both free and macroencapsulated islet 
      grafts.
PG  - 1269-83
LID - 10.3727/096368911X627408 [doi]
AB  - 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 beta-cell volume were evaluated. The effects of exendin-4 on 
      islet HIF-1alpha 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-1alpha 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-1alpha.
FAU - Jia, Xiaohui
AU  - Jia X
AD  - CLINTEC, Division of Transplantation Surgery, Karolinska Institutet, Karolinska 
      University Hospital, Stockholm, Sweden.
FAU - Sharma, Amit
AU  - Sharma A
FAU - Kumagai-Braesch, Makiko
AU  - Kumagai-Braesch M
FAU - Wernerson, Annika M
AU  - Wernerson AM
FAU - Sorenby, Anne K
AU  - Sorenby AK
FAU - Yamamoto, Shinji
AU  - Yamamoto S
FAU - Wang, Feng
AU  - Wang F
FAU - Tibell, Annika B
AU  - Tibell AB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120308
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Insulin)
RN  - 0 (Peptides)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Trans-Activators)
RN  - 0 (Venoms)
RN  - 0 (pancreatic and duodenal homeobox 1 protein)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9P1872D4OL (Exenatide)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Caspase 3/metabolism
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Cell Size/drug effects
MH  - Diabetes Mellitus, Experimental/metabolism/pathology/therapy
MH  - Endocrine System/*anatomy & histology
MH  - Exenatide
MH  - Homeodomain Proteins/metabolism
MH  - Hypoglycemic Agents/*pharmacology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Insulin/metabolism
MH  - Islets of Langerhans/cytology/*drug effects/metabolism
MH  - Islets of Langerhans Transplantation
MH  - Male
MH  - Peptides/*pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Trans-Activators/metabolism
MH  - Venoms/*pharmacology
EDAT- 2012/03/13 06:00
MHDA- 2013/05/02 06:00
CRDT- 2012/03/13 06:00
PHST- 2012/03/13 06:00 [entrez]
PHST- 2012/03/13 06:00 [pubmed]
PHST- 2013/05/02 06:00 [medline]
AID - ct0283jia [pii]
AID - 10.3727/096368911X627408 [doi]
PST - ppublish
SO  - Cell Transplant. 2012;21(6):1269-83. doi: 10.3727/096368911X627408. Epub 2012 Mar 
      8.