Protective effects of combined intervention with adenovirus vector mediated IL-10 and IGF-1 genes on endogenous islet β cells in nonobese diabetes mice with onset of type 1 diabetes mellitus.

Abstract

To investigate the protective effects of combined intervention with adenovirus vector mediated interleukin 10 (IL-10) and insulin-like growth factor 1 (IGF-1) genes on islet β cells in nonobese diabetes (NOD) mice with type 1 diabetes mellitus (T1D) at early stage. Twenty-four female NOD mice at onset of diabetes and aged 17-20 weeks old were randomly divided into four groups. Mouse 1, 2 and 3 groups were intraperitoneally injected 0.1 ml of Ad-mIGF-1, Ad-mIL-10, and combined Ad-mIGF-1 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 5 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, IGF-1, IFN-γ, IL-4 and C-peptide were measured and the degree of insulitis and the local expression of IGF-1 and IL-10 gene were observed. 1) IL-10 and IGF-1 levels in serum and pancreas were enhanced in 1, 2, and 3 groups; 2) serum INF-γ 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 3 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). The administration of adenovirus vector mediated IL-10 and/or IGF-1 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.