Journal
DIABETES
Volume 60, Issue 9, Pages 2350-2353Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db09-0490
Keywords
-
Categories
Funding
- Swedish Research Council [72XD-15043]
- Juvenile Diabetes Research Foundation
- AFA Insurance
- Swedish Diabetes Association
- Family Ernfors Fund
- Swedish Society for Medical Research
- David and Astrid Hagelens Foundation
- European Foundation for the Study of Diabetes/Novo Nordisk
- Novo Nordisk Foundation
Ask authors/readers for more resources
OBJECTIVE-No previous study has measured the oxygenation of intraportally transplanted islets, although recent data suggest that insufficient engraftment may result in hypoxia and loss of islet cells. RESEARCH DESIGN AND METHODS-After intraportal infusion into syngeneic mice, islet oxygenation was investigated in 1-day-old, 1-month-old, or 3-month-old grafts and compared with renal subcapsular grafts and native islets. Animals received an intravenous injection of pimonidazole for immunohistochemical detection of low-oxygenated islet cells (pO(2) <10 mmHg), and caspase-3 immunostaining was performed to assess apoptosis rates in adjacent tissue sections. RESULTS-In the native pancreas of nontransplanted animals, similar to 30% of the islets stained positive for pimonidazole. In 1-day-old and 1-month-old grafts, the percentage of pimonidazole-positive islets in the liver was twice that of native islets, whereas this increase was abolished in 3-month-old grafts. Beneath the renal capsule, pimonidazole accumulation was, however, similar to native islets at all time points. Apoptosis rates were markedly increased in 1-day-old intrahepatic grafts compared with corresponding renal islet grafts, which were slightly increased compared with native islets. One month posttransplantation renal subcapsular grafts had similar frequencies of apoptosis as native islets, whereas apoptosis in intraportally implanted islets was still high. In the liver, islet graft vascular density increased between 1 and 3 months posttransplantation, and apoptosis rates simultaneously dropped to values similar to those observed in native islets. CONCLUSIONS-The vascular engraflment of intraportally transplanted islets is markedly delayed compared with renal islet grafts. The prolonged ischemia of intraportally transplanted islets may favor an alternative implantation site. Diabetes 60:2350-2353, 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available