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. 2023 Oct 4;66(12):2292–2306. doi: 10.1007/s00125-023-06007-1

Fig. 7.

Fig. 7

Impaired beta cell function upon CSF1R inhibition can be partially restored by IL-1β. (a–e) Male wild-type mice were fed a PLX5622-containing diet or control diet from 4–5 weeks of age onwards, for up to 8.5 months. (a) Principal component (PC) analysis of normalised expression levels across the RNA-Seq samples of mice treated for either 5.5 months (5.5m) or 8.5 months (8.5m). (b) Gene set enrichment analysis of the C5 MSigDB collection (see ESM Table 4), performed on results of the differential expression analysis comparing islets isolated from mice fed a PLX5622-containing diet (n=7) or control diet (n=6); terms were considered significant if their associated false discovery rate (FDR) was below 5%. (c–e) Expression of immune cell markers and beta cell identity genes in islets from PLX5622-treated mice relative to control mice (n=10 for control diet; dotted line represents 1 [i.e. no change]). (f) Flow cytometry analysis of cytokine expression in islets macrophages incubated in 2 mmol/l or 20 mmol/l glucose. Cells were gated for macrophages using CD45, F4/80 and CD11b and macrophages were analysed for expression of IL-1β, TNF-α, IL-10, IFN-γ and IL-6. (g–m) Male wild-type mice were fed a PLX5622-containing diet or control diet from 8–10 weeks of age onwards, for 5 weeks. Data was obtained after 4 and 5 weeks of PLX treatment in a crossover study, with a 1 week wash-out period. Glucose levels during GTT (g–i) after administration of IL1–1β or saline (at time point −18 min) and corresponding insulin secretion (j–l) under the following conditions: control+saline vs PLX+saline (g, j); control+IL-1β vs control+saline (h, k); and PLX+IL-1β vs PLX+saline (i, l). (m) Fold change in insulin during GTT. Data are shown as mean±SEM and are representative of two independent experiments (a–f) or one experiment (g–m). For all graphs showing single data points (a, c–f, m), each data point represents an individual mouse, while all other graphs (b, g–l) show pooled data. PLX, PLX6522. *p<0.05, analysed by unpaired Mann–Whitney U test with two-tailed distribution, or two-way ANOVA (GTT)