Mechanisms of insulin resistance by simvastatin in C2C12 myotubes and in mouse skeletal muscle

Biochemical Pharmacology
Gerda M SanveeStephan Krähenbühl

Abstract

Statins inhibit cholesterol biosynthesis and lower serum LDL-cholesterol levels. They are generally well tolerated, but can cause insulin resistance in patients. Therefore, we investigated the mechanisms underlying the statin-induced insulin resistance. We used mice and C2C12 myotubes (murine cell line): mice (n = 10) were treated with oral simvastatin (5 mg/kg/day) or water (control) for 21 days and C2C12 cells were exposed to 10 μM simvastatin for 24 h. After intraperitoneal glucose application (2 g/kg), simvastatin-treated mice had higher glucose but equal insulin plasma concentrations than controls and lower glucose transport into skeletal muscle. Similarly, glucose uptake by C2C12 myotubes exposed to 10 μM simvastatin for 24 h was impaired compared to control cells. In simvastatin-treated C2C12 myotubes, mRNA and protein expression of the insulin receptor (IR) β-chain was increased, but the phosphorylation (Tyr1361) was impaired. Simvastatin decreased numerically Akt/PKB Thr308 phosphorylation (via insulin signaling pathway) and significantly Akt/PKB Ser473 phosphorylation (via mTORC2), which was explained by impaired phosphorylation of mTOR Ser2448. Reduced phosphorylation of Akt/PKB impaired downstream phosphorylation of...Continue Reading

Citations

May 17, 2019·Scientific Reports·Gerda M SanveeStephan Krähenbühl
Aug 29, 2019·Journal of Translational Medicine·Estela Lorza-GilHelena C F Oliveira
Jul 8, 2020·International Journal of Molecular Sciences·Unai Galicia-GarciaCésar Martín
Sep 19, 2020·Biomedicines·Miljenko Valentin PanajatovicJamal Bouitbir
Jun 3, 2021·International Journal of Molecular Sciences·Miljenko V PanajatovicJamal Bouitbir

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