Fig. 1. Long-term statins administration worsens insulin resistance in db/db mice.

All mice were ~50 weeks old. a Schematic diagram showing the procedure of long-term administration of statins for db/db mice. b Body weight. For 12 weeks, n = 6 biologically independent mice in Db/m group, n = 13 in Db group, n = 10 in Db + Ato5 group, n = 16 in Db + Ato10 group, n = 9 in Db + Rosu20 group. But over time, some of the mice gradually lost weight and died. By 43W, n = 6 biologically independent mice in Db/m group, n = 6 in Db group, n = 5 in Db + Ato5 group, n = 3 in Db + Ato10 group, n = 3 in Db + Rosu20 group. For specific values see as a “Source Data file”. c Kaplan–Meier survival curves of db/db mice after long-term administration of statin. Log-rank (Mantel–Cox) test was used for the analysis of statistical significance. Exact p value = 4 × 10⁻⁷. d Measurements of fasting blood glucose. n = 4 per time point. Significance **p < 0.01 compared with Db + Ato5 group, ^###p < 0.001 compared with Db + Ato10 group; e GHbA1c levels. n = 6 in each group. f ITT and AUC for db/db mice at 40 weeks. n = 4 per time point, and n = 5 per time point in Db + Ato5 group. g Immunohistochemical images of the RAGE in kidney sections. RAGE positive staining was mainly localized in the plasma membrane domains, and arrows represent RAGE expression in the cytoplasm of renal tubular epithelial cells⁴⁷. Original magnification ×400. Scale bar: 50 µm. All image part of the kidney was cortex. Renal structures indicated as proximal tubule (PT). h Quantitative analysis of expression of RAGE. n = 6 in each group. Data are expressed as means ± SEM (b, d, e, f, h). Significance tests were two-tailed, one-way ANOVA followed by Tukey’s test was performed (b, d–f, h). Source data are provided as a Source Data file.