Metformin attenuates palmitic acid-induced insulin resistance in L6 cells through the AMP-activated protein kinase/sterol regulatory element-binding protein-1c pathway

Wu,Wenjun; Tang,Sunyinyan; Shi,Junfeng; Yin,Wenwen; Cao,Shu; Bu,Ruifang; Zhu,Dalong; Bi,Yan

doi:10.3892/ijmm.2015.2187

Metformin attenuates palmitic acid-induced insulin resistance in L6 cells through the AMP-activated protein kinase/sterol regulatory element-binding protein-1c pathway

Authors:
- Wenjun Wu
- Sunyinyan Tang
- Junfeng Shi
- Wenwen Yin
- Shu Cao
- Ruifang Bu
- Dalong Zhu
- Yan Bi
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Affiliations: Department of Endocrinology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, P.R. China, Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu, P.R. China, Department of Oncology, Nanjing First Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China, Department of Endocrinology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, P.R. China
Published online on: April 17, 2015 https://doi.org/10.3892/ijmm.2015.2187
Pages: 1734-1740

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Abstract

AMP-activated protein kinase (AMPK) is an important effector of metformin action on glucose uptake in skeletal muscle cells. We recently reported that metformin improved insulin receptor substrate-1 (IRS-1)-associated insulin signaling by downregulating sterol regulatory element-binding protein‑1c (SREBP-1c) expression. In this study, we investigated whether AMPK activation and SREBP-1c inhibition contribute to the beneficial effects of metformin on IRS-1-associated insulin signaling in L6 myotubes. L6 muscle cells were incubated with palmitic acid (PA) to induce insulin resistance and then treated with metformin and/or the AMPK inhibitor, compound C. AMPK, SREBP-1c, IRS-1 and Akt protein expression levels were determined by western blot analysis. The effects of metformin on SREBP-1c gene transcription were determined by a luciferase reporter assay. Glucose uptake was evaluated using the 2-NBDG method. In the PA-treated L6 cells, metformin treatment enhanced AMPK phosphorylation, reduced SREBP-1c expression and increased IRS-1 and Akt protein expression, whereas treatment with compound C blocked the effects of metformin on SREBP-1c expression and the IRS-1 and Akt levels. Moreover, metformin suppressed SREBP-1c promoter activity and promoted glucose uptake through AMPK. The results from this study demonstrate that metformin ameliorates PA-induced insulin resistance through the activation of AMPK and the suppression of SREBP-1c in skeletal muscle cells.

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