This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted 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 Eizirik, D. L. Articles by Andersson, A. Search for Related Content PubMed PubMed Citation Articles by Eizirik, D. L. Articles by Andersson, A.

Mechanisms of Defective Glucose-Induced Insulin Release in Human Pancreatic Islets Transplanted to Diabetic Nude Mice¹

Department of Medical Cell Biology, Uppsala University, Biomedicum, Uppsala, Sweden

Address all correspondence and requests for reprints to: Dr. Décio L. Eizirik, Department of Metabolism and Endocrinology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. E-mail: deizirik{at}mebo.vub.ac.be

We have previously observed that human islets, transplanted under the kidney capsule of hyperglycemic nude mice, show a long-lasting impairment in glucose-induced insulin release. To investigate the cause(s) of this phenomenon, we transplanted human islets into normoglycemic or alloxan-diabetic nude mice for a 4- to 6-week period. In a third experimental group, aimed at evaluating reversibility of hyperglycemia effects, diabetic nude mice bearing a human islet graft were cured by a second intrasplenic transplant of mouse islets, and the human islets were exposed to a further 2 weeks of normoglycemia. Four to 6 weeks of hyperglycemia induced a severe impairment of glucose- and arginine-induced insulin release, as demonstrated by perfusion of the graft-bearing kidney. This defective release was not restored by a subsequent 2-week period of normoglycemia, and it was accompanied by normal (pro)insulin biosynthesis, glucose oxidation, and expression of insulin messenger RNA. Taken together with our previous study, these observations indicate that impaired glucose metabolism, depletion of insulin messenger RNA, decreased (pro)insulin biosynthesis, increased glycogen accumulation, and depletion of insulin reserves cannot explain the deleterious effects of the diabetic state on human islet insulin release. This, and the similar inhibition of glucose- and arginine-induced insulin release, suggest that prolonged hyperglycemia may exert its deleterious effect on insulin release at a step distal to closure of ATP-sensitive K-channels.

This article has been cited by other articles:

				M. Cnop, N. Welsh, J.-C. Jonas, A. Jorns, S. Lenzen, and D. L. Eizirik Mechanisms of Pancreatic {beta}-Cell Death in Type 1 and Type 2 Diabetes: Many Differences, Few Similarities Diabetes, December 1, 2005; 54(suppl_2): S97 - S107. [Abstract] [Full Text] [PDF]

				N. Kaiser, M. Yuli, G. Uckaya, A. I. Oprescu, M.-F. Berthault, C. Kargar, M. Y. Donath, E. Cerasi, and A. Ktorza Dynamic Changes in {beta}-Cell Mass and Pancreatic Insulin During the Evolution of Nutrition-Dependent Diabetes in Psammomys obesus: Impact of Glycemic Control Diabetes, January 1, 2005; 54(1): 138 - 145. [Abstract] [Full Text] [PDF]

				M. Biarnes, M. Montolio, V. Nacher, M. Raurell, J. Soler, and E. Montanya {beta}-Cell Death and Mass in Syngeneically Transplanted Islets Exposed to Short- and Long-Term Hyperglycemia Diabetes, January 1, 2002; 51(1): 66 - 72. [Abstract] [Full Text] [PDF]