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
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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