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GLP-1 contributes to increases in PGC-1α expression by downregulating miR-23a to reduce apoptosis.

Abstract：

:GLP-1 can help to overcome problems of liver cells metabolism, not only pancreatic cell. But the explicit mechanism of this effect remains unclear. In recent years, microRNAs have received the attention of researchers and some microRNAs have important implications for diabetes. The mitochondrial protective gene PGC-1α is also closely related to diabetes, and UCP2 is related to anti-mitochondrial oxidative stress, but the mechanism of action of these genes is unclear. In this study, we used HepG2 cell line and used the cell counting kit (CCK) to measure the cell viability with GLP-1(7-36) and/or glucotoxicity. To investigate alterations in gene expression resulting from incubation with GLP-1 (7-36) or hyperglycaemia, the RNA expression levels of miR-23a, PGC-1α, Bak, Bax and UCP2 were quantified using real-time PCR. The protein levels of PGC-1α were determined by western blot. The role of miR-23a in the regulation of PGC-1α was further assessed through cell transfection to downregulate of miR-23a expression. In this study, the viability of HepG2 hepatocytes was decreased under hyperglycaemia, but incubation with 10 nmol/L GLP-1 (7-36) amide for 24 h significantly increased the viability and decreased the mRNA expression levels of Bax and Bak. Incubation with GLP-1(7-36) amide for 24 h attenuated the RNA expression of miR-23a and increased the mRNA and protein expression of PGC-1α. Inhibition of miR-23a expression by cell transfection led to increases in the mRNA and protein expression of PGC-1α. In addition, the mRNA expression of UCP2 increased after incubation with GLP-1(7-36) for 24 h. In conclusion, GLP-1 induced increased expression of mitochondrial protective gene PGC-1α by downregulating miR-23a to inhibit hepatocyte apoptosis and also enhanced UCP2 to reduce apoptosis.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Wang C,Li Q,Wang W,Guo L,Guo C,Sun Y,Zhang J

doi

10.1016/j.bbrc.2015.08.092

subject

Has Abstract

pub_date

2015-10-09 00:00:00

pages

33-9

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(15)30482-4

journal_volume

466

pub_type

杂志文章

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GLP-1 contributes to increases in PGC-1α expression by downregulating miR-23a to reduce apoptosis.