This Article Full Text Full Text (PDF) All Versions of this Article: 144/7/3037    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Robitaille, R. Articles by Hallé, J.-P. Search for Related Content PubMed PubMed Citation Articles by Robitaille, R. Articles by Hallé, J.-P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Islet Cell Transplantation

Insulin-Like Growth Factor II Allows Prolonged Blood Glucose Normalization with a Reduced Islet Cell Mass Transplantation

Université de Montréal (R.R., J.D., N.H., J.-P.H.), Guy-Bernier Research Centre, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada H1T 2M4; and McGill University Health Center (L.R.), Montréal, Québec, Canada H3G 1A4

Address all correspondence and requests for reprints to: Jean-Pierre Hallé, M.D., Guy-Bernier Research Centre, Maisonneuve-Rosemont Hospital, 5415 boulevard de l’Assomption, Montréal, Québec, Canada H1T 2M4. E-mail: hallejp{at}videotron.ca.

IGF-II has been reported to decrease neonatal islet cell apoptosis and in vitro adult islet cell necrosis and apoptosis, but the usefulness of IGF-II in a transplantation setting is unknown. We evaluated the effect of in vitro IGF-II incubations on microencapsulated rat islet survival both in vitro and in minimal mass transplantations into diabetic mice. After 6 d in culture, fresh examinations, histology, fluorescence microscopy, sodium 3'-[1-(phenyl-amino-carbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro)-benzene sulfonic acid hydrate assay, and apoptosis studies all indicated that IGF-II significantly improves islet cell viability in a dose-dependent fashion. IGF-II 100 ng/ml and 500 ng/ml induced a 51% and 83% increase of viable islets (P = 0.052, P < 0.01). A 20%, 29%, and 33% reduction of the apoptotic index was observed with 50, 100, and 500 ng/ml incubations respectively (P < 0.05; P < 0.005; P < 0.001). Ten weeks after transplantation of 150 encapsulated rat islet equivalents incubated with IGF-II 500 ng/ml, 80% of diabetic mice were normoglycemic. Without IGF-II preincubation, only 8% of the recipients remained normoglycemic with the transplantation of 150 islets and 42% with 300 islets (P < 0.05). In conclusion, IGF-II promotes islet cell survival, and allows successful transplantation using a smaller number of islets.

This article has been cited by other articles:

				J. D. Rivas-Carrillo, A. Soto-Gutierrez, N. Navarro-Alvarez, H. Noguchi, T. Okitsu, Y. Chen, T. Yuasa, K. Tanaka, M. Narushima, A. Miki, et al. Cell-Permeable Pentapeptide V5 Inhibits Apoptosis and Enhances Insulin Secretion, Allowing Experimental Single-Donor Islet Transplantation in Mice Diabetes, May 1, 2007; 56(5): 1259 - 1267. [Abstract] [Full Text] [PDF]

				Y. Lu, A. Ponton, H. Okamoto, S. Takasawa, P. L. Herrera, and J.-L. Liu Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency and after streptozotocin-induced diabetes in mouse pancreas Am J Physiol Endocrinol Metab, July 1, 2006; 291(1): E50 - E58. [Abstract] [Full Text] [PDF]

				A. S. Narang and R. I. Mahato Biological and biomaterial approaches for improved islet transplantation. Pharmacol. Rev., June 1, 2006; 58(2): 194 - 243. [Abstract] [Full Text] [PDF]

				Y. Lu, P. L. Herrera, Y. Guo, D. Sun, Z. Tang, D. LeRoith, and J.-L. Liu Pancreatic-Specific Inactivation of IGF-I Gene Causes Enlarged Pancreatic Islets and Significant Resistance to Diabetes Diabetes, December 1, 2004; 53(12): 3131 - 3141. [Abstract] [Full Text] [PDF]

				N. Zhang, A. Richter, J. Suriawinata, S. Harbaran, J. Altomonte, L. Cong, H. Zhang, K. Song, M. Meseck, J. Bromberg, et al. Elevated Vascular Endothelial Growth Factor Production in Islets Improves Islet Graft Vascularization Diabetes, April 1, 2004; 53(4): 963 - 970. [Abstract] [Full Text] [PDF]