(Journal Article): beta-Cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia.
 
Biarnes M, Montolio M, Nacher V, Raurell M, Soler J, Montanya E (Laboratory of Diabetes and Experimental Endocrinology, Endocrine Unit, CSUB-Hospital de Bellvitge, University of Barcelona, Barcelona, Spain.)
 
IN: Diabetes 2002; 51(1):66–72.-
Impact Factor(s) of Diabetes: 8.848 (2004), 8.298 (2003), 8.256 (2002), 7.7 (2001)

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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.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Emamaullee JA, Rajotte RV, Liston P, Korneluk RG, Lakey JR, Shapiro AM, Elliott JF. XIAP overexpression in human islets prevents early posttransplant apoptosis and reduces the islet mass needed to treat diabetes. Diabetes 2005. 54: 2541-2548.
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