Fig. 2: Loss of hepatic Neuregulin1 impairs compensatory pancreatic islet hyperplasia in obese diabetic mice.

a, b Blood glucose (a) and plasma insulin (b) levels during an oral glucose tolerance test in liver-specific Neuregulin1 knockout (LNrg1 KO) and wild-type (WT) mice exposed 15 weeks to a high-fat/high-sucrose (HFHS) diet. Data represent mean ± SEM; n = 12 (blood glucose) and 11 (plasma insulin) mice per group. c Insulin tolerance test of LNrg1 KO and WT mice fed an HFHS for 15 weeks. Data represent mean ± SEM; n = 6 mice per group. No statistically significant differences were found between the two groups at any time point. d Immunoblotting of total and phosphorylated forms of AKT in indicated tissues of LNrg1 KO and WT mice fed an HFHS for 15 weeks. Tissues were harvested 15 min after insulin (0.75 IU/kg body weight) administration. This experiment was repeated three times independently using 6 mice of each group. e, f Representative H&E (e) and Ki-67 (f) staining of the pancreas of LNrg1 KO and WT mice fed either normal chow (NC) or an HFHS for 15 weeks. Islets are enclosed by dashed lines. Black arrowheads in (f) indicate Ki-67-positive cells. Scale bar, 50 μm. Quantification of islet area (r) and Ki-67-positive cell number (f). Data represent mean ± SEM; n = 5 (NC) and 9 (HFHS) mice per group, respectively. g Plasma Neuregulin1α (NRG1α) levels in LNrg1 KO and WT mice fed either an NC or an HFHS for 15 weeks. Data represent mean ± SEM; n = 6 (NC) and 7 (HFHS) mice per group. Unpaired Student’s t tests (a, b, c, e, and f) and a two-tailed Mann-Whitney U test (g) were performed.