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. 2022 Aug 12;13(6):2697–2711. doi: 10.1002/jcsm.13061

Figure 1.

Figure 1

Geranylgeranyl pyrophosphate (GGPP) depletion by statins inhibits glucose uptake in skeletal muscle cells in vitro and in vivo. (A) Mevalonate pathway. (B) C2C12 myotubes were pretreated with 10 μM simvastatin, 10 μM FTI‐277, 10 μM GGTI‐298, 1.5 mM 3‐PEHPC, and 1 mM perillyl alcohol for 24 h, then cells were exposed to 2‐NBDG containing 100 nM insulin for 30 min, and 2‐NBDG uptake was measured by fluorescence detection (n = 3). (C) C2C12 myotubes were treated with 10 μM GGPP, 10 μM simvastatin, and 10 μM GGPP combined with 10 μM simvastatin for 24 h, then cells were exposed to 2‐NBDG containing 100 nM insulin for 30 min, and 2‐NBDG uptake was measured by fluorescence detection (n = 3). (D–F) Male C57BL/6J mice (20 ± 2 g) were randomly grouped (n = 6). After administration of geranylgeraniol (GGOH) (25 mg/kg/day), simvastatin (40 mg/kg/day), and GGOH combined with simvastatin for 3 weeks, mice were subjected with experiments below. (D) Glucose tolerance test (GTT) and GTT AUC. (E) Insulin tolerance test (ITT) and ITT AUC. (F) After the measurement of GTT and ITT, mice were fasted for 16 h, and then mice were administrated with 2‐DG (2 g/kg body weight) via intraperitoneal injection. Mice were sacrificed 30 min later after the injection. The uptake of 2‐DG in gastrocnemius, tibialis anterior, soleus, and extensor digitorum longus was measured using Glucose Uptake Colorimetric Assay Kit. Data represented the mean ± SEM. Statistical analysis was performed with one‐way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.