Background: Type 1 diabetes (T1D) is an autoimmune disease (AID) whose primary features include progressive pancreatic β cell damage and absolute insufficient endogenous insulin secretion. Recent studies have shown that a Th1/Th2 cell subset unbalance and excessively activated B lymphocytes are important pathogenic mechanisms.
Objective and hypotheses: To investigate the protective effects of Adenovirus-mediated IL-10 gene and anti-CD20 monoclonal antibody (mAbs) on the pancreatic β cells in nonobese diabetes (NOD) mice with type 1 diabetes mellitus (T1D) at early stage.
Method: 35 female NOD mice at onset of diabetes and aged 1720 weeks old were randomly divided into 5 groups. Mouse 1, 2, 3, 4 and 5 groups were intravenously injected 500 ug of anti-CD20 mAbs, 500 ug of anti-CD20 mAbs combined with 100 ul of Ad-IL-10, 100 ul of Ad-IL-10, 100 ul of Ad-GFP, 100 ul of normal saline respectively. All mice were monitored for blood glycose everyday, and sacrificed 9 weeks after injection. Their serum levels of C-peptide were measured and the degree of insulitis were observed. Apoptosis related gene and protein were detected.
Results: (1) The blood glucose level of mice in group 2 was reduced, P<0.05. (2) A majority of the insulitis was grade 01 in group 2, and grade 23 in group 5. (3) The apoptosis rate of pancreatic β cells was significantly lower in group 2 than that in the group 3, 4, 5, P<0.05. (4) Immunohistochemistry indicated that IL-10 could be highly expressed locally in the pancreatic islets. (5) The results of qPCR and western blot showed that combined intervention exerted protective effects on pancreatic β cells through activating Bcl-2 anti-apoptosis pathway, inhibiting the expression of TNF-α and Fas, and blocking caspase-8caspase-3 as well as caspase-9caspase-3 apoptosis pathways.
Conclusion: Combined intervention could reduce the apoptosis of pancreatic β cells of NOD mice in the early stage of T1D, and had certain protective effects on the residual pancreatic β cell function.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology