Fig. 4: β cell-specific ErbB3 deletion impairs systemic glucose disposal and insulin secretion in obese diabetic mice.

a, b Immunoblots (a) and corresponding quantification (b) of total and phosphorylated forms of ERBBs, AKT, and ERK in the pancreas of normal mice injected with either PBS or recombinant protein encompassing the Neuregulin1 α type EGF-like domain (rNRG1α). TUBULIN served as a loading control. The average value of the ratio of phosphorylated to non-phosphorylated proteins in the samples of the PBS-treated group, normalized by the expression level of TUBULIN, was set to 1. Data represent mean ± SEM; n = 5 mice per group (b). The samples derive from the same experiment, and blots were processed in parallel. This experiment was repeated three times independently using5 mice of each group. c, d Immunoblots (c) and corresponding quantification (d) of total and phosphorylated forms of ERBB3 and ERK in the pancreas of normal mice fed a high-fat/high-sucrose (HFHS) diet for 15 weeks. β-ACTIN served as a loading control. The average value of the ratio of phosphorylated to non-phosphorylated proteins in the samples of normal mice fed a normal chow (NC), normalized by the expression level of β-ACTIN, was set to 1. Data represent mean ± SEM; n = 5 mice per group (d). e, f Blood glucose (e) and plasma insulin (f) levels after oral glucose challenge in β cell-specific ErbB3 KO (βErbB3KO) and WT mice fed an HFHS for 15 weeks. Data represent mean ± SEM; n = 12 (e) and 11 (f) mice per group. g, h. Representative H&E (g) and Ki-67 (h) staining of the pancreas of HFHS-treated WT and βErbB3KO mice. Islets were enclosed by the dashed line. Black arrowheads in (h) indicate Ki-67-positive cells. Scale bar, 50 μm. Quantification of islet area (g) and Ki-67-positive cell number (h). Data represent mean ± SEM; n = 11 (g) and 8 (h) mice per group. Unpaired Student’s t tests (b, d, e–h) were performed.