It is also possible that reduced Fingolimod insulin production or secretion is what allows them to maintain insulin sensitivity. Genetic studies are facilitated by the analysis of specific traits that arise due to genetic differences, as opposed to those that occur secondary to other changes. Thus, we examined whether WSB mice have alterations in b-cell mass or function that may contribute to these phenotypes. These studies revealed that WSB mice have reduced post-natal pancreatic growth that results in decreased b-cell mass in adults, and markedly enhanced insulin secretion from isolated islets in vitro. Decreased b-cell proliferation is recognized as a mechanism by which b-cell mass may become insufficient to meet the body’s needs, and many studies have examined b-cell development and proliferation of adult b-cells, e.g. in response to insulin resistance. Shortly after weaning, WSB mice had similar or even increased islet areas and b-cell mass compared to B6 mice. Despite the fact that WSB mice are,15–20% lighter than B6 mice at this age, they had similar pancreas weights. However, by 6-7 weeks of age, pancreatic weights were significantly lower in WSB mice compared to B6 mice. Whereas pancreatic weights increased 2.5 to 3-fold in B6 mice by 20 weeks of age, in WSB mice they increased only 20–50% during this timeframe. Yet islets from WSB mice did increase in size, with islet areas.10,000 mm2 by 20 weeks of age that were not apparent at 4 weeks of age, suggesting that postnatal islet growth does occur in WSB mice. At the older ages, insulin content and insulin staining areas per amount of pancreas were similar between the strains, suggesting a uniform change in both the endocrine and exocrine compartments. Adult WSB mice are smaller than B6 mice in terms of body weight and body length, and when pancreatic weights were normalized to body weight, they were similar between the strains. Combined, these data suggest that the difference in pancreatic weights between the strains may be reflective of different post-natal growth trajectories between the strains. b-cell mass has been shown to increase through development until roughly weaning, after which further expansion is thought to occur by proliferation, when required. However, pancreatic weights have been shown to continue to increase until,7 weeks of age in mice. Significant increases in pancreas weight postweaning have been observed in several species, yet less is known about this process. Alterations, for example, in Wnt signaling can lead to markedly increased pancreatic weights when normalized to body weight, whereas defective prolactin signaling may also be a mechanism of reduced pancreatic growth affecting both acinar and exocrine tissue. While factors affecting pancreatic development have been extensively studied, and while different mechanisms are known to affect b-cell proliferation during development and in adults, differences in post-natal pancreatic growth may be an under-appreciated determinant of adult b-cell mass.