Role of Wdr13 Gene in Beta Cell Proliferation Figure 2. Body weight, body composition, and glucose and insulin levels of Wdr13 knockout mice fed on normal chow and high fat diet. A) Growth curve of Wdr13+/0 male, Wdr132/0 male, Wdr13+/+ female, Wdr13+/2 female and Wdr132/2 female (n = 12) on normal chow. B) Increased adipose tissue mass in Wdr132/0 mice. C) H&E staining of a section of epididymal fat pad of Wdr132/0 mouse showing hypertrophy of adipose tissues D) Weight of epididymal fat pad in male and ovarian fat pad in female at 12 months (n = 6) of the mutant and wild type mice. E) Sixteen hours fasting glucose level in Wdr13 knockout mice at 2 months and 12 months. F) Random fed glucose level in Wdr13 knockout mice at 2 months and 12 months G) Fasting insulin level in Wdr13 knockout mice at 2 months and 12 months H) Random fed insulin level in Wdr13 knockout mice at 2 months and 12 months. I) Growth curve of Wdr13+/0 male and Wdr132/0 male on high fat diet (n = 10 to12). J) Fasting and fed insulin level in Wdr132/0 mice and in their wild type littermates at 6 months. (+/0 wild type male; 2/0 knockout male; +/+ wild type female; +/2 heterozygous female; 2/2 knockout female). doi:10.1371/journal.pone.0038685.g002 dependent higher body weight of the mutant mice advanced to five months when these mice were fed on a high fat diet (Figure 2I). Anatomical and histological examination revealed that the in- creased body weights of the mutant mice were mainly due to the increase in the adipose tissue volume/weight resulting from hypertrophy of adipocytes without any indication of change in adipocyte numbers (Figure 2C). Wdr13 knockout mice were mildly obese, and random insulin levels in these mice were ,2 fold higher as compared to their wild type littermates at 12 months on normal chow and at 6 months on a high fat diet. However, there was no difference in fasting insulin levels. Dynamic changes in the insulin-producing pancreatic beta cell mass are dependent on metabolic conditions, and positive correlations between body weight, insulin production and islet mass are well documented [12,32]. Various studies have shown that the increase in insulin levels may be a compensatory mechanism to the decreased peripheral insulin sensitivity in response to obesity, ultimately leading to islet failure and to type 2 diabetes [33]. On the other hand, it is also known that higher insulin levels result in higher glucose uptake by adipose tissues, PLoS ONE | www.plosone.org 4 June 2012 | Volume 7 | Issue 6 | e38685