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 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 micromol/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 approximately 60% (P < 0.05), whereas nonoxidative glucose disposal was increased by approximately 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.
Voshol
P J
PJ
TNO-Prevention and Health, Division VBO, Leiden, the Netherlands. pj.voshol@pg.tno.nl
Jong
M C
MC
Dahlmans
V E
VE
Kratky
D
D
Levak-Frank
S
S
Zechner
R
R
Romijn
J A
JA
Havekes
L M
LM
D000818:Animals; D001769:Blood / Q000378:metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology*; D012016:Reference Values; D014280:Triglycerides / Q000378:metabolism*
D007328:Insulin; D014280:Triglycerides; D006003:Glycogen; D003847:Deoxyglucose; D008071:Lipoprotein Lipase; D005947:Glucose