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Title: | B-cell death and mass in syngeneically transplanted islets exposed to short and long-term hyperglycemia |
Author: | Biarnés Costa, Montse Montolio Rusiñol, Marta Nacher, Victor Raurell, Mercè Soler Ramon, Joan Montanya Mias, Eduard |
Keywords: | Diabetis Cirurgia experimental Hiperglucèmia Illots de Langerhans Diabetes Experimental surgery Hyperglycemia Islands of Langerhans |
Issue Date: | Jan-2002 |
Publisher: | American Diabetes Association |
Abstract: | We studied the effects of hyperglycemia on beta-cell death and mass in syngeneically transplanted islets. Six groups of STZ-induced diabetic C57BL/6 mice were transplanted with 100 syngeneic islets, an insufficient beta-cell mass to restore normoglycemia. Groups 1, 2, and 3 remained hyperglycemic throughout the study. Groups 4, 5, and 6 were treated with insulin from day 7 before transplantation to day 10 after transplantation. After insulin discontinuation, group 6 mice achieved definitive normoglycemia. Grafts were harvested at 3 (groups 1 and 4), 10 (groups 2 and 5), and 30 (groups 3 and 6) days after transplantation. On day 3, the initially transplanted beta-cell mass (0.13 +/- 0.01 mg) was dramatically and similarly reduced in the hyperglycemic and insulin-treated groups (group 1: 0.048 +/- 0.002 mg; group 4: 0.046 +/- 0.007 mg; P < 0.001). Extensive islet necrosis (group 1: 30.7%; group 4: 26.8%) and increased beta-cell apoptosis (group 1: 0.30 +/- 0.05%; group 4: 0.42 +/- 0.07%) were found. On day 10, apoptosis remained increased in both hyperglycemic and insulin-treated mice (group 2: 0.44 +/- 0.09%; group 5: 0.48 +/- 0.08%) compared with normal pancreas (0.04 +/- 0.03%; P < 0.001). In contrast, on day 30, beta-cell apoptosis was increased in grafts exposed to sustained hyperglycemia (group 3: 0.37 +/- 0.03%) but not in normoglycemic mice (group 6: 0.12 +/- 0.02%); beta-cell mass was selectively reduced in islets exposed to hyperglycemia (group 3: 0.046 +/- 0.02 mg; group 6: 0.102 +/- 0.009 mg; P < 0.01). In summary, even in optimal conditions, approximately 60% of transplanted islet tissue was lost 3 days after syngeneic transplantation, and both apoptosis and necrosis contributed to beta-cell death. Increased apoptosis and reduced beta-cell mass were also found in islets exposed to chronic hyperglycemia, suggesting that sustained hyperglycemia increased apoptosis in transplanted beta-cells. |
Note: | Reproducció del document publicat a: https://doi.org/10.2337/diabetes.51.1.66 |
It is part of: | Diabetes, 2002, vol. 51, num. 1, p. 66-72 |
URI: | http://hdl.handle.net/2445/135009 |
Related resource: | https://doi.org/10.2337/diabetes.51.1.66 |
ISSN: | 0012-1797 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) |
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