Expression and regulation by insulin of low-density lipoprotein receptor-related protein mRNA in human skeletal muscle.
Evidence suggests that increased hydrolysis and/or uptake of triglyceride-rich lipoprotein particles in skeletal muscle can be involved in insulin resistance. We determined the steady state mRNA levels of the low-density lipoprotein-related receptor (LRP) and lipoprotein lipase (LPL) in skeletal muscle of eight healthy lean control subjects, eight type 2 diabetic patients and eight nondiabetic obese individuals. The regulation by insulin of LRP and LPL mRNA expression was also investigated in biopsies taken before and at the end of a 3 h euglycemic hyperinsulinemic clamp (insulinemia of about 1 nM). LRP mRNA was expressed in human skeletal muscle (1.3+/-0.1 amol/microg total RNA in control subjects). Type 2 diabetic patients, but not nondiabetic obese subjects, were characterized by a reduced expression of LRP (0.8+/-0.2 and 1.3+/-0.3 amol/microg total RNA in diabetic and obese patients, respectively; P<0.05 in diabetic vs. control subjects). Insulin infusion decreased LRP mRNA levels in muscle of the control subjects but not in muscle of type 2 diabetic and nondiabetic obese patients. Similar results were found when investigating the regulation of the expression of LPL. Taken together, these results did not support the hypothesis that a higher capacity for clearance or hydrolysis of circulating triglycerides in skeletal muscle is present during obesity- or type 2 diabetes-associated insulin resistance.
Boucher
Philippe
P
Department of Biochemistry, E. Herriot Hospital, Lyons, France.
Ducluzeau
Pierre Henri
PH
Davelu
Paul
P
Andreelli
Fabrizio
F
Vallier
Paulette
P
Riou
Jean Paul
JP
Laville
Martine
M
Vidal
Hubert
H
D000328:Adult; D003920:Diabetes Mellitus / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011973:Receptors, LDL