Signaling, stress response and apoptosis in pre-diabetes and diabetes: restoring immune balance in mice with alloxan-induced type 1 diabetes mellitus

Publication date: February 2016
Source:International Immunopharmacology, Volume 31
Author(s): Elena G. Novoselova, Olga V. Glushkova, Sergey M. Lunin, Maxim O. Khrenov, Tatyana V. Novoselova, Svetlana B. Parfenyuk, Evgeny E. Fesenko
The aim of this study was to compare immune imbalances in "pre-diabetic" and diabetic mice and to evaluate the efficacy of several agents in improving the immunity of mice with type 1 diabetes. Pre-diabetic and diabetic models generated by a single or double alloxan injection were monitored for plasma glucose and pancreas immunohistochemistry. To study the immunity in pre-diabetic and diabetic Balb/C male mice; the levels of cytokines; synthesis of inducible heat shock proteins HSP72 and HSP90α; activity of the NF-κB, IFR3, SAPK/JNK, and TLR4 pathways; and apoptosis levels in thymuses were measured. Pre-diabetes resulted in a decrease in IL-4, IL-5 and IL-10 in plasma; in diabetic mice, plasma IFN-gamma, IL-6, TNF-alpha, and IL-10 were decreased. The NF-κB alternative pathway activity and TLR4 expression were significantly increased only in pre-diabetic mice, whereas SAPK/JNK activation was observed at both stages of diabetes. Other measured parameters also showed distinct altered patterns in the immunity of pre-diabetic and diabetic mice. Treatment with an inhibitor of NF-κB, thymulin, or a diet with an antioxidant improved or normalized the immune balance in diabetic mice and also notably decreased pancreatic cell damage in pre-diabetic mice.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NX1fWm
via IFTTT