In Muscle-Specific Lipoprotein Lipase-Overexpressing Mice, Muscle Triglyceride Content Is Increased Without Inhibition of Insulin-Stimulated Whole-Body and Muscle-Specific Glucose Uptake
article
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 relation between intramuscular TG accumulation and insulin sensitivity. Therefore, in mice with muscle-specific overexpression of human lipoprotein lipase (LPL) and control mice, muscle TG content was measured in combination with glucose uptake in vivo, under hyperinsulinemic-euglycemic conditions. Overexpression of LPL in muscle resulted in accumulation of TGs in skeletal muscle (85.5 ± 33.3 vs. 25.7 ± 23.1 μmol/g tissue in LPL and control mice, respectively; P < 0.05). During the hyperinsulinemic clamp study, there were no differences in plasma glucose, insulin, and FFA concentrations between the two groups. Moreover, whole-body, as well as skeletal muscle, insulin-mediated glucose uptake did not differ between LPL-overexpressing and wild-type mice. Surprisingly, whole-body glucose oxidation was decreased by ∼60% (P < 0.05), whereas nonoxidative glucose disposal was increased by ∼50% (P < 0.05) in LPL-overexpressing versus control mice. In conclusion, overexpression of human LPL in muscle increases intramuscular TG accumulation, but does not affect whole-body or muscle-specific insulin-mediated uptake, findings that argue against a simple causal relation between intramuscular TG content and insulin resistance. Chemicals/CAS: Deoxyglucose, 154-17-6; Glucose, 50-99-7; Glycogen, 9005-79-2; Insulin, 11061-68-0; Lipoprotein Lipase, EC 3.1.1.34; Triglycerides
Topics
TNO Identifier
236271
ISSN
00121797
Source
Diabetes, 50(7-12), pp. 2585-2590.
Pages
2585-2590
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