Abstract
ObjectiveTo 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.MethodsTwenty-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.Results1) 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).ConclusionThe 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.
Highlights
Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by insufficient insulin secretion and progressive damage of islet b-cells [1,2]
We have previously found that combined with transgenic technology, insulin-secreting cells that overexpress IL10 by in vitro infection of Ad-rIL-10 still have insulin secretion function even at high glucose condition [17]
Ad-mIL-10 and Ad-mIGF-1 with titer of 1.06109 pfu/mL were kindly provided by Professor Zhihong Chen of the Department of Pediatrics, the Affiliated Hospital of Medical College Qingdao University
Summary
Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by insufficient insulin secretion and progressive damage of islet b-cells [1,2]. Its incidence is increasing worldwide in children [3]. T1D is caused by the interactions between genetic predisposition [4,5] and environmental factors [6,7,8,9]. It has been demonstrated to be a T cell-mediated disease. A current hypothesis is that B-cell play an immportant role in the development of T1D by regulate T-cells [10]. Th2 cytokines (in particular IL-10), which could inhibit the function of Th1 cells and activity of Th1 cytokines, are considered as effective therapeutic factors for T1D [14,15]
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