Development of low-dose streptozotocin-induced diabetes in ICAM-1-deficient mice.
Multiple injections of low-dose streptozotocin (LDSZ) induce immune-mediated insulitis and diabetes in C57BL/6 (H-2b) 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 H2b 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.
Martin
S
S
Clinical Department, German Diabetes Research Institute at the Heinrich-Heine University Düsseldorf. martin@dfi.uni-duesseldorf.de
Vinke
A
A
Heidenthal
E
E
Schulte
B
B
van den Engel
N
N
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001786:Blood Glucose; D004276:DNA, Satellite / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D016296:Mutagenesis; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013311:Streptozocin / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D001786:Blood Glucose; D004276:DNA, Satellite; D018799:Intercellular Adhesion Molecule-1; D013311:Streptozocin