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Cell Journal، جلد ۱۳، شماره Supplement، صفحات ۰-۰
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عنوان انگلیسی O-8: Leukocyte Antigen-Related (LAR) Knock down Improves Palmitate induced Insulin Resistancein C2C12 Muscle Cells
چکیده انگلیسی مقاله Objective: Type 2 diabetes is the most common disorder that results from two defects, insulin resistance and beta cell dysfunction. Skeletal muscle accounts for approximately 70-80% of insulin dependent glucose uptake in the body. At the molecular and cellular levels, there is a connection between fatty acid accumulation and insulin resistance in this tissue, but the exact mechanism is poorly understood. Protein tyrosine phosphatases are the key elements of insulin signaling that potentially can be a candidate in FFA induced insulin resistance. In the present study we have focused on the role of Leukocyte common antigen-related (LAR), in insulin resistance induced by palmitate by knocking down LAR gene in mouse skeletal cells. Materials and Methods: Mouse skeletal C2C12 cells were differentiated into myotubes. Myotubes were treated with 0.25 and 0.5mM conjugated palmitate for 16h. RNA was isolated and cDNA were synthesized. Real Time PCR and western blot analysis were performed. The designed shRNA against LAR was cloned into pSilencer and the the vectors were transfected to cells. Glucose uptake assay was also performed in the treated myotubes. Results: There was no significant difference in mRNA and protein levels of LAR between 0.25mM palmitate in comparison with untreated cells. 0.5 mM palmitate significantly induced LAR mRNA and protein levels in myotubes compared to the untreated cells (45%,p< 0.01, 48%,p< 0.01, respectively). shRNA reduced LAR expression around 55% in protein level. Reduction of LAR improveed glucose uptake significantly, but at the presence of palmitate glucose uptake was less than the absence of palmitate. Conclusion: Findings of this study can reveal that palmitate can be one of the responsible factors inducing LAR expression in the muscle of diabetic patients. Knocking down of LAR improves insulin resistance in skeletal muscle even when palmitate is present.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/1516
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