Details

Autor(en) / Beteiligte

• Zheng, Jie
• Wang, Kuansong
• Jin, Ping
• Dong, Changsheng
• Yuan, Qiong
• Li, Yuanjian
• Yang, Zhichun

Titel

The association of adipose-derived dimethylarginine dimethylaminohydrolase-2 with insulin sensitivity in experimental type 2 diabetes mellitus

Ist Teil von

• Acta biochimica et biophysica Sinica, 2013-08, Vol.45 (8), p.641-648

Ort / Verlag

China

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Asymmetric dimethylarginine （ADMA） is an endogenous inhibitor of nitric oxide synthase （NOS）, which can be hydrolyzed by dimethylarginine-dimethylaminohydrolase （DDAH）. It has been reported that adipocytes can produce DDAH/ADMA, but its role remains unknown. In the present study, we examined the effects of adipocyte-derived DDAH/ADMA on insulin sensitivity using animal and cell models. Results showed that in adipose tissue of high fat diet-fed diabetic rats, as well as in high glucose （25 mM） plus insulin （100nM）-treated 3T3-L1 adipocytes, expression levels of insulin receptor substance-1 （IRS-1）, glucose trans- porter-4 （GLUT-4）, and DDAH isoform-2 （DDAH-2） were down-regulated compared with control, although DDAH-1 expression showed no significant changes. We also observed that nitric oxide bioavailability, DDAH and NOS activities were subsequently decreased, while the local ADMA content was elevated in diabetic adipose tissue. Transfection of human DDAH-2 gene into high glucose- and insulin-treated 3T3-L1 adipocytes significantly ameliorated DDAH activity, reduced ADMA contents, and up-regulated the mRNA ex- pression levels of IRS-1 and GLUT-4. These findings sug- gested that in the development of type 2 diabetes meHitus, local DDAH-2 in adipocytes might play an important role in regulating insulin sensitivity.