Development of low-dose streptozotocin-induced diabetes in ICAM-1-deficient mice

Multiple injections of low-dose streptozotocin (LDSZ) induce immune-mediate d insulitis and diabetes in C57BL/6 (H-2(b)) mice. To evaluate the role of the intercellular adhesion molecule-1 (ICAM-1) for LDSZ induced immune-medi ated diabetes, we have investigated mice genetically deficient in the ICAM- 1 gene (ICAM-1(-/-)) in comparison to wild-type (ICAM-1(+/+)) mice. ICAM-1( -/-) mice, which had a mixed genetic bacl<ground of C57BL/6 and DBA/2 mice, were backcrossed to C57BL/6 mice and screened for H2(b) homogenicity. Mice received five daily injections of 40 mg/kg streptozotocin. On day 21 after the first LDSZ injection 55% of the ICAM-1(+/+) (female 33%, male 80%) and 50 % of the ICAM-1(-/-) (female 20 %, male 100 %), mice had blood glucose levels over 200 mg/dl. Mean blood glucose levels increased in response to L DSZ treatment, however, no differences between ICAM-1(+/+) and ICAM-1(-/-) mice were noted. Histological examinations of pancreatic islets revealed mo nonuclear infiltration of pancreatic islets without significant differences between both groups of mice. In summary, LDSZ-induced immune-mediated insu litis and diabetes development occurs in ICAM-1(-/-) mice similarly than in ICAM-1(+/+) mice. These results do not support the hypothesis that ICAM-1 plays a key role during immune-mediated infiltration and destruction of pan creatic islets in LDSZ induced diabetes.