title: Signaling, stress response and apoptosis in pre-diabetes and diabetes: restoring immune balance in mice with alloxan-induced type 1 diabetes mellitus.
abstract: 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.
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Elena G
authors.initials: EG
authors.lastname: Novoselova
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Glushkova
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia. Electronic address: lunin@pochta.ru.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Lunin
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Maxim O
authors.initials: MO
authors.lastname: Khrenov
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Novoselova
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Svetlana B
authors.initials: SB
authors.lastname: Parfenyuk
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Evgeny E
authors.initials: EE
authors.lastname: Fesenko
mesh_terms: D000496:Alloxan / Q000008:administration & dosage; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D013935:Thymic Factor, Circulating / Q000008:administration & dosage* / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D000496:Alloxan; D013935:Thymic Factor, Circulating; D048055:Mitogen-Activated Protein Kinase 8
keywords: Antioxidants; Caspase-3; Cytokines; Heat-shock proteins; IKK Inhibitor XII; NF-κB; SAPK/JNK; Thymulin; Type 1 diabetes