Transgenic expression of antioxidant protein thioredoxin in pancreatic beta cells prevents progression of type 2 diabetes mellitus.
The authors previously established a transgenic mouse line in the type 1 diabetes model, NOD mouse, in which thioredoxin (TRX), a redox protein, is overexpressed in pancreatic beta cells, and found that TRX overexpression slows the progression of type 1 diabetes. Recent reports on type 2 diabetes suggest that oxidative stress also degrades the function of beta cells. To elucidate whether TRX overexpression can prevent progressive beta cell failure from oxidative stress in type 2 diabetes, the authors transferred the TRX transgene from the NOD mouse onto a mouse model of type 2 diabetes, the db/db mouse. The progression of hyperglycemia and the reduction of body weight gain and insulin content of the db/db mouse were significantly suppressed by the TRX expression. Furthermore, TRX suppressed the reduction of Pdx-1 and MafA expression in the beta cells, which may be one of the cellular mechanisms for protecting beta cells from losing their insulin-secreting capacity. These results showed that TRX can protect beta cells from destruction not only in type 1 but also in type 2 diabetes, and that they provide evidence that oxidative stress plays a crucial role in the deterioration of beta cell function during the progression of type 2 diabetes.
Yamamoto
Mayu
M
Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan.
Yamato
Eiji
E
Toyoda
Shu-Ichi
S
Tashiro
Fumi
F
Ikegami
Hiroshi
H
Yodoi
Junji
J
Miyazaki
Jun-Ichi
J
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism*; D051473:Maf Transcription Factors, Large / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism
D001786:Blood Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D013879:Thioredoxins