The involvement of Ca 2+ in the insulin-mediated signaling cascade, resulting in glucose uptake in skeletal muscle, is uncertain. Here, we test the hypothesis that Ca 2+ influx through canonical transient receptor potential 3 (TRPC3) channels modulates insulin-mediated glucose uptake in adult skeletal muscle. Experiments were performed on adult skeletal muscle cells of wild-type (WT) and obese, insulin-resistant ob / ob mice. Application of the diacylglycerol analog 1-oleyl-2-acetyl-sn-glycerol (OAG) induced a nonselective cation current, which was inhibited by the addition of anti-TRPC3 antibody in the patch pipette and smaller in ob / ob than in WT cells. Knockdown of TRPC3, using a novel technique based on small interfering RNA (siRNA) coupled to functionalized carbon nanotubes, resulted in pronounced (∼70%) decreases in OAG-induced Ca 2+ influx and insulin-mediated glucose uptake. TRPC3 and the insulin-sensitive glucose transporter 4 (GLUT4) coimmunoprecipitated, and immunofluorescence staining showed that they were colocalized in the proximity of the transverse tubular system, which is the predominant site of insulin-mediated glucose transport in skeletal muscle. In conclusion, our results indicate that TRPC3 interacts functionally and physically with GLUT4, and Ca 2+ influx through TRPC3 modulates insulin-mediated glucose uptake. Thus, TRPC3 is a potential target for treatment of insulin-resistant conditions.—Lanner, J. T., Bruton, J. D., Assefaw-Redda, Y., Andronache, Z., Zhang, S.-J., Severa, D., Zhang, Z.-B., Melzer, W., Zhang, S.-L., Katz, A., Westerblad, H. Knockdown of TRPC3 with siRNA coupled to carbon nanotubes results in decreased insulin-mediated glucose uptake in adult skeletal muscle cells.
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Knockdown of TRPC3 with siRNA coupled to carbon nanotubes results in decreased insulin-mediated glucose uptake in adult skeletal muscle cells
Lanner, Johanna T.; Bruton, Joseph D.; Assefaw-Redda, Yohannes; Andronache, Zoita; Zhang, Shi-Jin; Severa, Denise; Zhang, Zhi-Bin; Melzer, Werner; Zhang, Shi-Li; Katz, Abram; Westerblad, Håkan
Follow The FASEB Journal
, Volume 23 (6): 1728
Fed of American Socs for Experimental Biology – Jun 1, 2009
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