Selenium acts as an insulin-like molecule for the down-regulation of diabetic symptoms via endoplasmic reticulum stress and insulin signalling proteins in diabetes-induced non-obese diabetic mice.
To investigate whether selenium (Sel) treatment would impact on the onset of diabetes,we examined serum biochemical components including glucose and insulin,endoplasmic reticulum (ER) stress and insulin signalling proteins, hepatic C/EBP-homologous protein (CHOP) expression and DNA fragmentation in diabetic and non- diabetic conditions of non-obese diabetic (NOD) mice. We conclude that (i) Sel treatment induced insulin-like effects in lowering serum glucose level in Sel-treated NOD mice, (ii) Sel-treated mice had significantly decreased serum biochemical components associated with liver damage and lipid metabolism, (iii) Sel treatment led to the activation of the ER stress signal through the phosphorylation of JNK and eIF2 protein and insulin signal mechanisms through the phosphorylation of Akt and PI3 kinase, and (iv) Sel-treated mice were significantly relieved apoptosis of liver tissues indicated by DNA fragmentation assay in the diabetic NOD group. These results suggest that Sel compounds not only serve as insulin-like molecules for the downregulation of glucose level and the incidence of liver damage, but may also have the potential for the development of new drugs for the relief of diabetes by activating the ER stress and insulin signalling pathways.
Hwang
Daeyoun
D
Laboratory Animal Resources Team, National Institute of Toxicological Research, Korea FDA, Seoul 122-704, Korea. dyhwang@kfda.go.kr
Seo
Sujin
S
Kim
Yongkyu
Y
Kim
Chuelkyu
C
Shim
Sunbo
S
Jee
Seungwan
S
Lee
Suhae
S
Jang
Mikyong
M
Kim
Minsun
M
Yim
Suyoun
S
Lee
Sang-Koo
SK
Kang
Byeongcheol
B
Jang
Insurk
I
Cho
Jungsik
J
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction
D001786:Blood Glucose; D007328:Insulin; D012643:Selenium