Role of Wdr13 Gene in Beta Cell Proliferation Figure 3. Glucose tolerance test (GTT) and Insulin tolerance test (ITT) of Wdr13 knockout mice. A) GTT at 2 months on normal chow (n = 8–12). B) GTT at 12 months on normal chow (n = 8–10). C) Glucose tolerance test at 6 months on high fat diet (n = 8). D) ITT at 2 months on normal chow (n = 8–12). E) ITT at 12 months on normal chow (n = 8–10). F) Insulin tolerance test at 6 months on high fat diet (n = 8) G) ITT at 9 months on high fat diet (n = 6–8). (+/0 wild type male; 2/0 knockout male). doi:10.1371/journal.pone.0038685.g003 which would in turn alter the lipid metabolism and adipogenesis [34]. Consistent with the latter findings, insulin receptor knockout mice exhibited decreased adipose tissue [35]. Insulin stimulates hepatic lipogenesis as well as fatty acid uptake in adipocytes leading to increased adipose tissue formation [27]. Moreover, insulin receptor glucose transporter-4 pathway helps to convert glucose to lipid in adipose tissues [34]. In addition to the role of insulin in adipogenesis, insulin secretion has been positively correlated with obesity in humans [19], rodents [20] and non mammalian avian models [36]. In Wdr13 knockout mice, islet mass, insulin levels and glucose-stimulated insulin secretion were more at 6 months on a high fat diet. Notwithstanding higher body weights at 6 month and onwards, the mutant mice had better glucose clearance, without any indication of diabetes till the termination of experiments at 9 months of age in the case of a high fat diet and 12 months on normal chow (Figure 3). Further, ITT experiments showed similar insulin sensitivity in Wdr13 knockout mice as their wild type littermates. However, the lack of insulin resistance as revealed by ITT data would require confirmation using hyperinsulinemic clamp studies. Nevertheless, it appears that the body weight gain in Wdr13 knockout mice may be a consequence of insulin hypersecretion, which in turn may alter adipogenesis in fat cells. Hyperinsulinemia, accompanied by mild obesity in Wdr13 knockout mice appears to be reminiscent of MOR1 [26] and chop [25,31] knockout mice, where adiposity is enhanced by higher insulin secretion. It may be recalled that Wdr13 gene is expressed at high levels in brain and at moderate levels in liver and adipose tissues (Figure 1). Therefore, we cannot PLoS ONE | www.plosone.org 5 June 2012 | Volume 7 | Issue 6 | e38685