Simvastatin-Induced Insulin Resistance May Be Linked to Decreased Lipid Uptake and Lipid Synthesis in Human Skeletal Muscle: the LIFESTAT Study
Autor: | Jørn Wulff Helge, Steen Larsen, Clara Prats, Flemming Dela, Sune Dandanell, Andreas Vigelsø |
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Rok vydání: | 2018 |
Předmět: |
Adult
Blood Glucose Leptin Male 0301 basic medicine Simvastatin medicine.medical_specialty Article Subject Endocrinology Diabetes and Metabolism Hypercholesterolemia 030204 cardiovascular system & hematology lcsh:Diseases of the endocrine glands. Clinical endocrinology Impaired glucose tolerance 03 medical and health sciences 0302 clinical medicine Endocrinology Insulin resistance Internal medicine medicine Humans Glucose homeostasis Muscle Skeletal Glucose tolerance test Lipoprotein lipase lcsh:RC648-665 medicine.diagnostic_test Chemistry nutritional and metabolic diseases Skeletal muscle Lipid metabolism Glucose Tolerance Test Middle Aged Lipid Metabolism medicine.disease 030104 developmental biology medicine.anatomical_structure Clinical Study lipids (amino acids peptides and proteins) Adiponectin Hydroxymethylglutaryl-CoA Reductase Inhibitors Insulin Resistance medicine.drug |
Zdroj: | Journal of Diabetes Research Journal of Diabetes Research, Vol 2018 (2018) |
ISSN: | 2314-6753 2314-6745 |
Popis: | 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. |
Databáze: | OpenAIRE |
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