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Polymyxin B, scavenger of endotoxin, enhances isolation yield and in vivo function of islets

Cited 5 time in Web of Science Cited 6 time in Scopus
Authors
Park, Sang G.; Kim, Jae H.; Oh, Ji H.; Lee, Han N.; Chung, Sung S.; Lee, Yeon Y.; Park, Kyong S.; Jung, Hye S.; Lee, Ye J.; Park, Ho S.
Issue Date
2010-03
Publisher
WILEY-BLACKWELL PUBLISHING, INC
Citation
TRANSPLANT INTERNATIONAL; Vol.23 3; 325-332
Keywords
endotoxinIslets of Langerhanspolymyxin Bglucose-stimulated insulin releasetransplantation
Abstract
Collagenase purified from bacteria has been used to isolate islets for transplantation. However, collagenase is contaminated with small amounts of endotoxin, which induces dysfunction or apoptosis of islets. In this study, we investigated the effects of polymyxin B, endotoxin scavenger, on the yield and quality of isolated islets. It is revealed that polymyxin B neutralized endotoxin in vitro and inhibited endotoxin-mediated decreases of the glucose stimulation index. Additionally, adenosine triphosphate (ATP) quantitation, islet regression assay, and caspase-3 activation assay demonstrated that polymyxin B efficiently blocked the toxic effects induced by endotoxin. Thereafter, we isolated mouse islets both with and without polymyxin B and compared total islet equivalents (IEQs), glucose-stimulated insulin release, and ATP content. Polymyxin B enhanced islet recovery, and ATP content of islets, and glucose stimulation index, and reduced TNF-alpha expression of islets. Marginal transplantation (200 IEQs/mouse) under the kidney capsule of diabetic mice induced normoglycemia in 30% of the polymyxin B group, but not in any mouse of control group. This result suggests that islets isolated with polymyxin B more effectively lower blood glucose levels as compared with control islets. Thus, polymyxin B could serve as a useful agent in the protection of islets from endotoxin-induced inflammation and apoptosis.
ISSN
0934-0874
Language
English
URI
http://hdl.handle.net/10371/76536
DOI
https://doi.org/10.1111/j.1432-2277.2009.00987.x
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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