Knockdown of LYRM1 Rescues Insulin Resistance and Mitochondrial Dysfunction Induced by FCCP in 3T3-L1 Adipocytes
| Autor: | Jin-Gai Zhu, Xin-Guo Cao, Min Zhang, Guan-zhong Zhu, Jie Qiu, Zhen-Ying Qin, Ya-Ping Zhao, Xirong Guo, Chunmei Shi, Chenbo Ji, Yu-Mei Wang, Yong-mei Dai |
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| Rok vydání: | 2014 |
| Předmět: |
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
medicine.medical_specialty Glucose uptake Biophysics Mitochondrion Biology Biochemistry Mice chemistry.chemical_compound Adenosine Triphosphate Insulin resistance 3T3-L1 Cells Internal medicine Adipocytes medicine Animals Insulin Phosphorylation Protein kinase B Membrane Potential Mitochondrial Glucose Transporter Type 4 Tyrosine phosphorylation Cell Biology General Medicine medicine.disease Mitochondria Protein Transport Insulin receptor Glucose Endocrinology chemistry Gene Knockdown Techniques Proton Ionophores biology.protein Insulin Resistance Apoptosis Regulatory Proteins Reactive Oxygen Species GLUT4 Signal Transduction |
| Zdroj: | Cell Biochemistry and Biophysics. 70:667-675 |
| ISSN: | 1559-0283 1085-9195 |
| DOI: | 10.1007/s12013-014-9971-y |
| Popis: | LYR motif-containing 1 (LYRM1) was recently discovered to be involved in adipose tissue homeostasis and obesity-associated insulin resistance. We previously demonstrated that LYRM1 overexpression might contribute to insulin resistance and mitochondrial dysfunction. Additionally, knockdown of LYRM1 enhanced insulin sensitivity and mitochondrial function in 3T3-L1 adipocytes. We investigated whether knockdown of LYRM1 in 3T3-L1 adipocytes could rescue insulin resistance and mitochondrial dysfunction induced by the cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP), a mitochondrion uncoupler, to further ascertain the mechanism by which LYRM1 is involved in obesity-associated insulin resistance. Incubation of 3T3-L1 adipocytes with 1 µM FCCP for 12 h decreased insulin-stimulated glucose uptake, reduced intracellular ATP synthesis, increased intracellular reactive oxygen species (ROS) production, impaired insulin-stimulated Glucose transporter type 4 (GLUT4) translocation, and diminished insulin-stimulated tyrosine phosphorylation of Insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Protein Kinase B (Akt). Knockdown of LYRM1 restored insulin-stimulated glucose uptake, rescued intracellular ATP synthesis, reduced intracellular ROS production, restored insulin-stimulated GLUT4 translocation, and rescued insulin-stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt in FCCP-treated 3T3-L1 adipocytes. This study indicates that FCCP-induced mitochondrial dysfunction and insulin resistance are ameliorated by knockdown of LYRM1. |
| Databáze: | OpenAIRE |
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