Department of Newborn Infants, Nanjing Children's Hospital of Nanjing Medical University, Nanjing, China.
J Bioenerg Biomembr. 2012 Dec;44(6):665-71. doi: 10.1007/s10863-012-9472-x. Epub 2012 Sep 12.
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.
NYGGF4（也称为 PID1）是一个最近发现的基因，它与肥胖相关的胰岛素抵抗（IR）有关。我们旨在本研究中通过在 3T3-L1 脂肪细胞中用二甲双胍处理，进一步阐明 NYGGF4 对 IR 的影响及其潜在机制。我们的数据表明，二甲双胍预处理可通过增加 NYGGF4 过表达脂肪细胞中 GLUT4 向质膜的易位，显著增强胰岛素刺激的葡萄糖摄取。NYGGF4 过表达导致 IRS-1 的酪氨酸磷酸化和 Akt 的丝氨酸磷酸化显著抑制，而二甲双胍孵育可强烈激活 NYGGF4 过表达脂肪细胞中 IRS-1 和 Akt 的磷酸化。NYGGF4 过表达脂肪细胞中的活性氧（ROS）水平显著增加，二甲双胍预处理可降低其水平。我们的数据还表明，二甲双胍增加了 PGC1-α、NRF-1 和 TFAM 的表达，而 NYGGF4 过表达脂肪细胞中这些基因的表达减少。这些结果表明，NYGGF4 在 IR 中发挥作用，其对 IR 的影响可通过激活 IRS-1/PI3K/Akt 和 AMPK-PGC1-α 途径被二甲双胍逆转。
