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Published on: June 25, 2017
Leukocyte antigen-related inhibition attenuates palmitate-induced insulin resistance in muscle cells
Sattar Gorgani-Firuzjaee1, Salar Bakhtiyari, Abolfazl Golestani
1Department of Biochemistry, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
Abstract:
Palmitate has been shown to induce insulin resistance in skeletal muscle cells. The aim of this study was to investigate the role of the leukocyte common antigen-related (LAR) gene in palmitate-induced insulin resistance in C2C12 cells. A stable C2C12 cell line was generated using LAR short hairpin RNA. The levels of LAR protein and phosphorylation of insulin receptor substrate-1 (IRS1) and Akt were detected by western blot analysis. 2-Deoxyglucose uptake was measured in LAR knockdown and control cells using d-[2-(3)H]glucose. LAR protein level was decreased by 65% in the stable cell line compared with the control cells. Palmitate (0.5 mM) significantly induced LAR mRNA (65%) and protein levels (40%) in myotubes compared with untreated cells. Palmitate significantly reduced insulin-stimulated glucose uptake in both the control and LAR knockdown cells by 33 and 51% respectively. However, LAR depletion improved insulin-stimulated glucose uptake in myotubes treated with palmitate. Furthermore, the inhibition of LAR prevented palmitate-induced decreases in phosphorylation of IRS1(Tyr632) and Akt(Ser473) in C2C12 cells. In conclusion, these results reveal that palmitate induces LAR expression in C2C12 cells. We also provided evidence that the inhibition of LAR attenuates palmitate-induced insulin resistance in myotubes.
Insights
Palmitate causes insulin resistance in muscle cells by increasing LAR gene expression. Inhibiting the leukocyte common antigen-related (LAR) gene improves insulin sensitivity, offering a potential therapeutic target for metabolic disorders.
Area of Science:
- Molecular Biology
- Cell Biology
- Metabolic Research
Background:
- Palmitate is known to induce insulin resistance in skeletal muscle.
- The leukocyte common antigen-related (LAR) gene's role in this process is not fully understood.
Purpose of the Study:
- To investigate the role of the LAR gene in palmitate-induced insulin resistance in C2C12 skeletal muscle cells.
- To determine if inhibiting LAR expression can ameliorate palmitate-induced insulin resistance.
Main Methods:
- Generated a stable C2C12 cell line with reduced LAR expression using short hairpin RNA.
- Analyzed LAR protein levels, insulin receptor substrate-1 (IRS1) and Akt phosphorylation via western blot.
- Measured 2-deoxyglucose uptake using radiolabeled glucose in LAR knockdown and control cells.
Main Results:
- Palmitate treatment significantly increased LAR mRNA and protein levels in C2C12 myotubes.
- LAR depletion partially restored insulin-stimulated glucose uptake in palmitate-treated cells.
- Inhibition of LAR prevented palmitate-induced decreases in IRS1 and Akt phosphorylation.
Conclusions:
- Palmitate induces LAR expression in C2C12 cells, contributing to insulin resistance.
- Inhibiting LAR expression attenuates palmitate-induced insulin resistance in skeletal muscle cells.
- LAR represents a potential therapeutic target for managing palmitate-induced insulin resistance.
