statin treatment  (Cegedim Strategic Data Medical Research Ltd)

Journal: Cell reports

Article Title: Hepatocyte Rap1a contributes to obesity- and statin-associated hyperglycemia

doi: 10.1016/j.celrep.2022.111259

Figure Lengend Snippet: (A and B) Primary mouse hepatocytes (HCs) were treated with vehicle, 10 μM simvastatin (simva), or simvastatin + geranylgeranyl pyrophosphate (GGPP) (10 μM) for 24 h. Membrane proteins were assayed for Rap1a and pan-cadherin (pan-CDH, loading control) (A), and forskolin and dexamethasone (F + D)-induced G6pc and Pck1 mRNA levels were measured (B) (n = 2–3 biological replicates, mean ± SEM, *p < 0.05). (C–G) DIO mice were fed with a high-fat diet containing 0.02% simvastatin (w/w) for 12 weeks. Mice were then administered with geranylgeraniol (GGOH, 100 mg/kg/day) or vehicle control by daily gavage for 3 weeks while still receiving the statin-containing diet. Overnight fasting blood glucose (C), glucose tolerance test (D), liver G6pc and Pck1 mRNA (E), body weight before and after simvastatin and GGOH treatment (F), and overnight fasting plasma insulin (G) were assayed (n = 5–7 mice/group, mean ± SEM, *p < 0.05, n.s., non-significant). (H) Primary mouse hepatocytes that were transfected with si-Pggt1b (encoding GGT1) or scrambled control (scr) were assayed for Pggt1b , and F + D-induced G6pc and Pck1 mRNA levels (n = 3 biological replicates, mean ± SEM, *p < 0.05). (I–L) Liver Pggt1b mRNA (I), 5-h fasting blood glucose (J), body weight before and after AAV injection (K), and 5-h fasting plasma insulin (L) levels were assayed from DIO mice that were injected with AAV8 vectors containing shRNA against Pggt1b (sh-Pggt1b) or empty, control AAV8 (Con) (n = 7 mice/group, mean ± SEM, *p < 0.05, n.s., non-significant). See also – .

Article Snippet: For statin treatment experiments, 18-week-old male DIO mice (Jackson Labs, stock number: 380050) were fed a high-fat diet containing 0.02% (w/w) simvastatin (Research Diets, cat #D12492) for 12 weeks.

Techniques: Membrane, Control, Clinical Proteomics, Transfection, Injection, shRNA