Wdr13 and streptozotocin-induced diabetes

Abstract

Type I diabetes, though contributes to only 5-10% of total diabetes cases, is a rising concern in today's world. Our previous studies have shown that the absence of WDR13 in mouse results in pancreatic β-cell hyper-proliferation. Also, amelioration of the diabetic phenotype on introgression of Wdr13-null (Wdr13^-/0) mutation in genetically diabetic mice (Lepr^db/db) [type II diabetes] was observed. It was thus, interesting to see the role of WDR13 in streptozotocin-mediated diabetes in mice, a model for type I diabetes. Wdr13^-/0 mice along with its wild type (Wdr13^+/0 mice) littermates were administered streptozotocin intraperitoneally for 5 consecutive days. Blood glucose levels and body weights of these mice were monitored for subsequent 5 weeks and then they were sacrificed for physiological and histological analyses. Results showed that Wdr13^-/0 mice exhibited higher serum insulin levels, better glucose clearance and significantly higher number of proliferating β-cells; reiterating the finding that absence of WDR13 helps in β-cell hyper-proliferation and recovery from diabetes; further underscoring WDR13 as a key target molecule for diabetes treatment/amelioration.

Fig. 1

a Weekly blood glucose levels of vehicle and STZ treated Wdr13^+/0 and Wdr13^-/0 mice. b Gain in body weight of animals treated with vehicle and STZ. c Glucose tolerance test of vehicle treated animals. d Glucose tolerance test of STZ treated animals. e Fasting glucose levels of vehicle and STZ treated animals. f Serum insulin levels of vehicle and STZ treated Wdr13^+/0 and Wdr13^-/0 mice at the end of the experiment. n = 3 for vehicle treated animals, n = 8 for STZ treated animals. *p < 0.05, ***p < 0.001

Fig. 2

a Histological analyses of pancreatic sections by hematoxylin-eoisin (H&E) staining, immunostaining with Ki-67 . b Average islet area of vehicle and STZ treated Wdr13^+/0 and Wdr13^-/0 mice, determined by Axioskop software. c Percentage Ki-67 positive cells in STZ treated Wdr13^+/0 and Wdr13^-/0 mice. *p < 0.05, **p < 0.01, ***p < 0.001.