Oral administration of insulin to female nonobese diabetic mice inhibited diabetes and induced Fas ligand expression on islets of Langerhans

OBJECTIVE: To detect oral administration of recombinant human insulin to nonobese diabetic (NOD) mice for preventing them from diabetes and insulitis and to detect the effects of oral administration of insulin on Fas and Fas ligand expression on islet of Langerhans. METHODS: Sixty-four female NOD mice were divided into two groups. One group (34) was orally administered recombination human insulin 1 mg in 500 microliters PBS and the other (30) 500 microliters PBS only at age of 5 weeks old, twice a week for the first week, then weekly until 30 weeks of age. RESULTS: Oral administration of insulin to female NOD mice can significantly suppress diabetes and insulitis. The insulitis was less severe in the group fed with insulin than that in the control group (score of insulitis: 1.25 +/- 0.45 vs 3.0 +/- 0.76 at 16 weeks of age, P < 0.01). We examined Fas ligand and Fas expression on islets of Langerhans in both groups of NOD mice by using immunohistochemical techniques. We find that Fas only expressed on islets when the mice suffered the diabetes, whereas Fas ligand expressed on islets of the mice fed with insulin at 16 and 20 week of ages. We did not find Fas ligand positive staining on the islet feeding with PBS. CONCLUSION: We speculated that oral insulin may induce Fas ligand expression on the islets and plays a role in protecting the pancreatic beta-cell from autoimmune destruction. These results show that oral insulin affected autoimmune diabetes and insulitis in NOD mice. The immune mechanism of oral tolerance is closely related to the change of Fas ligand and Fas system.