Fig. 8
Neratinib improves glycemia, insulin secretion, and β-cell survival in obese db/db mouse model of type 2 diabetes. Obese diabetic Leprdb/db mice on the C57BLKS/J background (db/db) were randomized in two groups at the age of 6 weeks, and then, neratinib or vehicle was daily i.p. injected at a concentration of 5 mg/kg throughout the whole experiment of 31 days. a Random fed blood glucose measurements before and after 31 days of Neratinib or vehicle injection (last day of the study). b Intraperitoneal glucose tolerance test (ipGTT). c, d Intraperitoneal insulin tolerance test (ipITT). In d, basal glucose values were normalized to 100% (respective area-under-the-curve (AUC) analyses for b and d are shown in the right insets). e Insulin secretion during an ipGTT measured before (0 min) and 15 min after glucose injection. f The ratio of secreted insulin and glucose is calculated at fed state. Data are representative of six mice per group (n = 6 for (a–f)). g–j Mice were killed at day 31. g β-cell mass (given as percentage of the whole pancreatic section from ten sections spanning the width of the pancreas; n = 5 mice/group) and quantitative analyses from triple stainings for (h) TUNEL, (i) Ki67, (j) pHH3, and (k) nuclear PDX1 expression, insulin, and DAPI expressed as percentage of TUNEL-, Ki67-, pHH3-, or nuclear PDX1-positive β-cells ± SEM. An average number of 13667 (h), 5937 (i), 7108 (j), or 4330 (k) β-cells were counted from n = 3–5 (h, i, k) or n = 5–6 (j) mice/group. Data show means ± SEM. *p < 0.05 vehicle control at the end (10.5 weeks of age) compared with the start of the study (6 weeks of age), **p < 0.05 db/db compared with db/db-Nera injected mice; by one-way ANOVA with Bonferroni corrections for (a); by Student’s t tests for (b–k). Source data are provided as a Source Data file
