Pioglitazone has direct effects on insulin sensitivity and intracellular lipid content in L6 skeletal muscle cells

Using L6 skeletal muscle cell line, rendered insulin resistant by incubation with triglyceride-rich lipoproteins (TGRLs), we sought to answer the question whether pioglitazone has direct effects on this cell line. Incubation of L6 cells with TGRLs led to an increase in the intramyocellular triglyceride content. Moreover, TGRLs led to a reduction in insulin-stimulated glycogen content and GSK-3 phosphorylation. All these changes induced by TGRLs could be antagonized by incubation of L6 cells with pioglitazone. The PPAR-γ antagonist GW9662 reversed the pioglitazone effects. We conclude that pioglitazone has direct insulin-sensitizing effects on the L6 skeletal muscle cell line, which are paralleled by a reduction in intramyocellular triglyceride accumulation.