Development of Low-Dose Streptozotocin-Induced Diabetes in ICAM-1-Deficient Mice

Abstract

Multiple injections of low-dose streptozotocin (LDSZ) induce immune-mediated 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-mediated 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 background 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 LDSZ treatment, however, no differences between ICAM-1^+/+ and ICAM-1^-/- mice were noted. Histological examinations of pancreatic islets revealed mononuclear infiltration of pancreatic islets without significant differences between both groups of mice. In summary, LDSZ-induced immune-mediated insulitis 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 pancreatic islets in LDSZ induced diabetes.

Key words

Low-dose Streptozotocin Diabetes - ICAM-I - ICAM-I Deficient Mice