NYGGF4 ( PID1) effects on insulin resistance are reversed by metformin in 3T3-L1 adipocytes

Qiu, Jie; Wang, Yu-mei; Shi, Chun-mei; Yue, Hong-ni; Qin, Zhen-Ying; Zhu, Guan-zhong; Cao, Xin-guo; Ji, Chen-bo; Cui, Yan; Guo, Xi-rong
December 2012
Journal of Bioenergetics & Biomembranes;Dec2012, Vol. 44 Issue 6, p665
Academic Journal
NYGGF4 (also called PID1) is a recently discovered gene that is involved in obesity-related insulin resistance (IR). We aimed in the present study to further elucidate the effects of NYGGF4 on IR and the underlying mechanisms through using metformin treatment in 3T3-L1 adipocytes. Our data showed that the metformin pretreatment strikingly enhanced insulin-stimulated glucose uptake through increasing GLUT4 translocation to the PM in NYGGF4 overexpression adipocytes. NYGGF4 overexpression resulted in significant inhibition of tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, whereas incubation with metformin strongly activated IRS-1 and Akt phosphorylation in NYGGF4 overexpression adipocytes. The reactive oxygen species (ROS) levels in NYGGF4 overexpression adipocytes were strikingly enhanced, which could be decreased by the metformin pretreatment. Our data also showed that metformin increased the expressions of PGC1-α, NRF-1, and TFAM, which were reduced in the NYGGF4 overexpression adipocytes. These results suggest that NYGGF4 plays a role in IR and its effects on IR could be reversed by metformin through activating IRS-1/PI3K/Akt and AMPK-PGC1-α pathways.


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