Mitochondrial nutrients improve immune dysfunction in the type 2 diabetic Goto-Kakizaki rats.
The development of type 2 diabetes is accompanied by decreased immune function and the mechanisms are unclear. We hypothesize that oxidative damage and mitochondrial dysfunction may play an important role in the immune dysfunction in diabetes. In the present study, we investigated this hypothesis in diabetic Goto-Kakizaki rats by treatment with a combination of four mitochondrial-targeting nutrients, namely, R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide and biotin. We first studied the effects of the combination of these four nutrients on immune function by examining cell proliferation in immune organs (spleen and thymus) and immunomodulating factors in the plasma. We then examined, in the plasma and thymus, oxidative damage biomarkers, including lipid peroxidation, protein oxidation, reactive oxygen species, calcium and antioxidant defence systems, mitochondrial potential and apoptosis-inducing factors (caspase 3, p53 and p21). We found that immune dysfunction in these animals is associated with increased oxidative damage and mitochondrial dysfunction and that the nutrient treatment effectively elevated immune function, decreased oxidative damage, enhanced mitochondrial function and inhibited the elevation of apoptosis factors. These effects are comparable to, or greater than, those of the anti-diabetic drug pioglitazone. These data suggest that a rational combination of mitochondrial-targeting nutrients may be effective in improving immune function in type 2 diabetes through enhancement of mitochondrial function, decreased oxidative damage, and delayed cell death in the immune organs and blood.
Hao
Jiejie
J
Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China.
Shen
Weili
W
Tian
Chuan
C
Liu
Zhongbo
Z
Ren
Jinmin
J
Luo
Cheng
C
Long
Jiangang
J
Sharman
Edward
E
Liu
Jiankang
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000097:blood; D007155:Immunologic Factors / Q000097:blood; D042541:Intracellular Space / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013482:Superoxide Dismutase / Q000097:blood; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D001798:Blood Proteins; D007155:Immunologic Factors; D008055:Lipids; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione; D002118:Calcium