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

Horm Metab Res. 1999 Dec;31(12):636-40. doi: 10.1055/s-2007-978812.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Blood Glucose
  • DNA, Satellite / analysis
  • Diabetes Mellitus, Experimental / genetics*
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Female
  • Flow Cytometry
  • Genotype
  • Intercellular Adhesion Molecule-1 / analysis
  • Intercellular Adhesion Molecule-1 / genetics*
  • Leukocytes, Mononuclear / chemistry
  • Leukocytes, Mononuclear / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout*
  • Mutagenesis
  • Pancreas / cytology
  • Pancreas / drug effects
  • Pancreas / immunology
  • Streptozocin / pharmacology

Substances

  • Antibiotics, Antineoplastic
  • Blood Glucose
  • DNA, Satellite
  • Intercellular Adhesion Molecule-1
  • Streptozocin