In muscle-specific lipoprotein lipase-overexpressing mice, muscle triglyceride content is increased without inhibition of insulin-stimulated whole-body and muscle-specific glucose uptake

In patients with type 2 diabetes, a strong correlation between accumulation of intramuscular triclycerides (TGs) and insulin resistance has been found . The aim of the present study was to determine whether there is a causal r elation between intramuscular TG accumulation and insulin sensitivity. Ther efore, in mice with muscle-specific overexpression of human lipoprotein lip ase (LPL) and control mice, muscle TG content was measured in combination w ith glucose uptake in vivo, under hyperinsulinemic-euglycemic conditions. O verexpression of LPL in muscle resulted in accumulation of TGs in skeletal muscle (85.5 +/- 33.3 vs. 25.7 +/- 23.1 mu mol/g tissue in LPL and control mice, respectively; P < 0.05). During the hyperinsulinemic clamp study, the re were no differences in plasma glucose, insulin, and FFA concentrations b etween the two groups. Moreover, whole-body, as well as skeletal muscle, in sulin-mediated glucose uptake did not differ between LPL-overexpressing and wild-type mice. Surprisingly, whole-body glucose oxidation was decreased b y similar to 60% (P < 0.05), whereas nonoxidative glucose disposal was incr eased by -50% (P < 0.05) in LPL-overexpressing versus control mice. In conc lusion, overexpression of human LPL in muscle increases intramuscular TG ac cumulation, but does not affect whole-body or muscle-specific insulin-media ted uptake, findings that argue against a simple causal relation between in tramuscular TG content and insulin resistance.