PubMed2000
OBJECTIVES: To study whether recombinant human (rhIGF-1) can prevent the onset of type 1 diabetes in female non-obese diabetic (NOD) mice, and its influence on their immune system. METHODS: Ten mice were injected intraperitonally (i.p.) rhIGF-1 37.5 micrograms.kg-1.d-1 at 4 weeks old for 2 weeks at treated group; and the same volume of normal solution (NS) was used in 10 mice as control group. All mice were killed at 40 weeks old or 2 weeks after the diagnosis of diabetes. Blood glucose of tail vein blood was measured weekly using a glucometer. At the end of the experiment, serum C-peptide levels and antibodies to glutamic acid decarboxylase (GAD) were detected with RIA and ELISA methods, respectively. T cell subsets of spleen were undertaken two-color FACS analysis using Cy-chrome anti-CD4 and FITC-anti-CD8 monoclonal antibodies; pancreatic histopathology and immunohistochemistry of T cell were conducted. RESULTS: Treatment with rhIGF-1 at 4 weeks old reduced the total incidence of diabetes (40% vs 90%, P < 0.05) and delay its onset [(26.25 +/- 3.68) weeks vs (21.6 +/- 6.7) weeks] compared with control group (P < 0.05). RhIGF-1 showed the growth effect on NOD mice, because the wet weight of spleen and pancreas of groups treated with rhIGF-1 were higher than that of control mice (P < 0.01, respectively). Only 3.24 (0.92 islets/mouse) was observed in the control group at death, but they increased to 13.2 (3.14 islets/mouse) in the rhIGF-1 group. The insulitis score decreased from 0.738 +/- 0.194 to 0.098 +/- 0.035 in the later group. A marked reduction of insulitis severity of pancreatic glands was also observed. A strong proliferative response of CD8+ T subsets in splenocytes occurred in rhIGF-1 treated mice, and the imbalance of CD4+/CD8+ subgroup in control mice (2.03 +/- 0.72) was corrected in the later group (0.53 +/- 0.22, respectively, P < 0.01). The lymphocytes infiltrating islets in the rhIGF-1 group showed a reduction of CD4+ cells, and they existed only outside of islets. CONCLUSIONS: These data demonstrated the preventive effects of rhtIGF-1 on the onset of type 1 diabetes and the severity of insulitis in female NOD mice. The mechanisms of these effects may be related to the induction of a CD8+ Ts cell response that inhibits the spontaneous development of autoreactive CD4+ T subsets response, or inhibiting the homing of CD4+ T cells to islets.