[Effect of metformin on the expression of SIRT1 and UCP2 in rat liver of type 2 diabetes mellitus and nonalcoholic fatty liver].
OBJECTIVE
To observe the effect of metformin on the expression of SIRT1 and UCP2 in rat liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD), and discuss the pathogenesis of T2DM with NAFLD, and the treatment with and possible mechanism of metformin.


METHODS
Thirty-six male SD rats were randomly divided into a normal control group (group NC, n=12), a T2DM with NAFLD group (group MC, n=12), and a metformin group (group A, n=12). We established the model of T2DM with NAFLD rats by feeding high-fat and high-sugar diet and injecting STZ. After the success establishment of the model, the metformin group was given metformin 300 mg/(kg.d) for 8 weeks. At the end of the experiment, we measured FBG, ALT, AST, TC, TG, HDL-C, LDL-C, VLDL, FFAs, FINs and HOMA-IR respectively in group NC, MC and A. We observed the change of liver tissue pathology by HE, determined the expression of SIRT1 and UCP2 in rat liver by immunohistochemical method and real-time quantitative method.


RESULTS
FBG, ALT, AST, TC, TG, LDL-C, VLDL, FFAs, FINs and HOMA-IR were higher in group MC than in group NC (P<0.05), while HDL-C was obviously lower in group MC than in group NC (P<0.05). After the metformin treatment, the serum parameters in the rats had improved in group NC compared with in group MC (P<0.05). On immunohistochemical staining and mRNA level, the expression of SIRT1 was obviously lower in group MC than in group NC (P<0.05), and the expression of UCP2 was obviously higher in group MC than in group NC (P<0.05). After the metformin treatment, the expression of SIRT1 was higher than in group MC (P<0.05), and the expression of UCP2 was lower than in group MC (P<0.05). There was negative correlation between the expression of SIRT1 and UCP2 (r=-0.61, P<0.01).


CONCLUSIONS
The expression of SIRT1 is low and the expression of UCP2 is high in rat liver of T2DM with NAFLD. Metformin can increase the expression of SIRT1 and reduce the expression of UCP2, with negative correlation between the expression of SIRT1 and UCP2.
Department of Endocrinology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004,China xujingjdey85@163.com.
Jing
J
Xu
Nan
N
Li
Junhong
J
Wang
Chunhong
C
Zhang
Shimei
S
Ding
Yang
Y
Jiao
Jing
J
Zhang
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000378:metabolism*; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D008687:Metformin; C488368:Sirt1 protein, rat; D056564:Sirtuin 1