TY - JOUR
T1 - Simvastatin-Induced Insulin Resistance May Be Linked to Decreased Lipid Uptake and Lipid Synthesis in Human Skeletal Muscle
T2 - the LIFESTAT Study
AU - Larsen, Steen
AU - Vigelsø, Andreas
AU - Dandanell, Sune
AU - Prats, Clara
AU - Dela, Flemming
AU - Helge, Jørn Wulff
PY - 2018
Y1 - 2018
N2 - Background: A prevalent side-effect of simvastatin is attenuated glucose homeostasis. The underlying mechanism is unknown, but impaired lipid metabolism may provide the link. The aim of this study was to investigate whether simvastatin-treated patients had a lower capacity to oxidize lipids and reduced expression of the major proteins regulating lipid uptake, synthesis, lipolysis, and storage in skeletal muscle than matched controls.Materials and Methods: Ten men were treated with simvastatin (HbA1c: 5.7 ± 0.1%), and 10 healthy men (HbA1c: 5.2 ± 0.1%) underwent an oral glucose tolerance test and a muscle biopsy was obtained. Fat oxidation rates were measured at rest and during exercise. Western blotting was used to assess protein content.Results: Patients treated with simvastatin had impaired glucose tolerance compared with control subjects, but fat oxidation at rest and during exercise was compatible. Skeletal muscle protein content of CD36, lipoprotein lipase (LPL), and diacylglycerol acyltransferase (DGAT) 1 were lower, and DGAT 2 tended to be lower in patients treated with simvastatin.Conclusions: Patients treated with simvastatin had a reduced capacity to synthesize FA and diacylglycerol (DAG) into triacylglycerol in skeletal muscle compared to matched controls. Decreased lipid synthesis capacity may lead to accumulation of lipotoxic intermediates (FA and DAG) and hence impair glucose tolerance.
AB - Background: A prevalent side-effect of simvastatin is attenuated glucose homeostasis. The underlying mechanism is unknown, but impaired lipid metabolism may provide the link. The aim of this study was to investigate whether simvastatin-treated patients had a lower capacity to oxidize lipids and reduced expression of the major proteins regulating lipid uptake, synthesis, lipolysis, and storage in skeletal muscle than matched controls.Materials and Methods: Ten men were treated with simvastatin (HbA1c: 5.7 ± 0.1%), and 10 healthy men (HbA1c: 5.2 ± 0.1%) underwent an oral glucose tolerance test and a muscle biopsy was obtained. Fat oxidation rates were measured at rest and during exercise. Western blotting was used to assess protein content.Results: Patients treated with simvastatin had impaired glucose tolerance compared with control subjects, but fat oxidation at rest and during exercise was compatible. Skeletal muscle protein content of CD36, lipoprotein lipase (LPL), and diacylglycerol acyltransferase (DGAT) 1 were lower, and DGAT 2 tended to be lower in patients treated with simvastatin.Conclusions: Patients treated with simvastatin had a reduced capacity to synthesize FA and diacylglycerol (DAG) into triacylglycerol in skeletal muscle compared to matched controls. Decreased lipid synthesis capacity may lead to accumulation of lipotoxic intermediates (FA and DAG) and hence impair glucose tolerance.
KW - Adiponectin/blood
KW - Adult
KW - Blood Glucose/metabolism
KW - Glucose Tolerance Test
KW - Humans
KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
KW - Hypercholesterolemia/drug therapy
KW - Insulin Resistance/physiology
KW - Leptin/blood
KW - Lipid Metabolism/drug effects
KW - Male
KW - Middle Aged
KW - Muscle, Skeletal/drug effects
KW - Simvastatin/pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85054063208&partnerID=8YFLogxK
U2 - 10.1155/2018/9257874
DO - 10.1155/2018/9257874
M3 - Journal article
C2 - 30276217
AN - SCOPUS:85054063208
VL - 2018
JO - Journal of Diabetes Research
JF - Journal of Diabetes Research
SN - 2314-6745
M1 - 9257874
ER -