Fig. 5: FFAR4-mediated IL-6-dependent insulin secretion is compromised in type-2 diabetic mice.

a Body weight of Ffar4^flox/flox (control, n = 12) and LysM-Cre;Ffar4^flox/flox (My-Ffar4-KO, n = 11) mice fed with high-fat diet (HFD). b Blood glucose levels after glucose injection in control (n = 12) and My-Ffar4-KO (n = 11) mice fed with HFD. c Body weight of Il6ra^flox/flox (control, n = 6) and Ins1-CreERT2;Il6ra^flox/flox (β-cell-Il6ra-KO, n = 8) mice fed with HFD. d Blood glucose levels after glucose injection in control (n = 6) and β-cell-Il6ra-KO (n = 8) mice fed with HFD. e Numbers of islet F4/80⁺ cells (macrophages) from wild-type mice (n = 6) fed with either normal-chow diet (ND) or HFD. f and g, Ffar4 (f), and Il6 (g) mRNA levels in islet macrophages isolated from ND- or HFD-fed wild-type mice (n = 6). All data were normalized to GAPDH and were expressed relative to the average level in macrophages from mice fed with ND. h TUG-891-induced IL-6 release from islets from wild-type mice (n = 8) fed with either ND or HFD (left panel). The right panel shows the total islet IL-6 content from ND- or HFD-fed wild-type mice (n = 5). Results were normalized to islet protein levels. i and j, Effect of TUG-891 (i; n = 8) or IL-6 (j; n = 8/6/7/6/8/6/7/6) on insulin secretion from islets isolated from wild-type mice fed with either ND or HFD at different glucose levels. Results were normalized to islet protein levels. k TUG-891-induced changes in the intracellular Ca²⁺ concentration ([Ca²⁺]_i) in islet macrophages from wild-type mice fed with either ND or HFD. Arrows indicate the time point when TUG-891 or ionomycin was added. The data are shown as % of peak response to ionomycin. The bar diagram shows the area under the curve (AUC) of TUG-891-induced Ca²⁺ transients as % of the ionomycin-induced Ca²⁺ transient. 46 islet macrophages from ND-fed mice (n = 3) and 49 islet macrophages from HFD-fed mice (n = 3) were analyzed. Shown are mean values ± SEM; P-values are given in the figure; n.s.: not significant (Bonferroni’s two-way ANOVA test (a–d, h (left panel), i–k (left panel)), unpaired parametric two-tailed Student t test (e–h (right panel)), unpaired non-parametric two-tailed Mann-Whitney U test (k (right panel)). Source data are provided as a Source Data file.