Introduction: To investigate the protective effects of combined intervention with adenovirus vector mediated interleukin 10 (IL-10) and insulin-like growth factor 1 (IGF1) genes on islet β cells in nonobese diabetes (NOD) mice with type 1 diabetes mellitus (T1D) at early stage.
Methods: Twenty-four female NOD mice at onset of diabetes and aged 1720 weeks old were randomly divided into four groups. Mouse 1, 2 and 3 groups were intraperitoneally injected 0.1 ml of Ad-mIGFIGF11, Ad-mIL-10, and combined Ad-mIGF1 and Ad-mIL-10, respectively. Mouse 4 group were used as diabetes control. In addition, six age- and sex-matched non-diabetic NOD mice were intraperitoneally injected 0.1 ml of PBS and assigned five group as normal controls. All mice were weekly monitored for body weight, urine glucose and blood glycose, and sacrificed 3 weeks after injection. Their serum levels of IL-10, IGF1, IFN-γ, IL-4 and C-peptide were measured and the degree of insulitis and the local expression of IGF1 and IL-10 gene were observed.
Results: 1) IL-10 and IGF1 levels in serum and pancreas were enhanced in 1, 2, and 3 groups; 2) serum INFγ level was decreased while serum IL-10 and IL-4 levels were increased in 1, 2 and 3 groups, and these alterations were more significant in three group than 1 and 2 groups (P<0.01); 3) C-peptide level was not enhanced in 1 group, but significantly increased in 2 and 3 groups, and these increases were more significant in the latter (P<0.01); 4) Three weeks later, the body mass of mice in 2 and 3 groups decreased significantly (P<0.05).
Conclusion: The administration of adenovirus vector mediated IL-10 and/or IGF1 gene showed limited immune regulatory and protective effects on islet β-cells in NOD mice with T1D at early stage, and no significant reduction in insulitis, blood glucose and body weight.
Funding information: The project was sponsored by the National Natural Science Foundation of China (81170762) and Shandong Province Natural Science Foundation (Y2008C50).
01 - 03 Oct 2015
European Society for Paediatric Endocrinology