The cWnt activator, Rspondin-1 (Rspo1), has been identified as a regulator of β-cell growth and function, although its role in pathophysiological conditions such as streptozotocin (STZ)-induced diabetes is unknown. Hence, I hypothesized that Rspo1 deficiency stimulates β-cell neogenesis in STZ-diabetes. There was no difference in oral glucose handling between STZ-induced Rspo1mice, although, Rspo1-/- mice demonstrated increased insulin sensitivity compared to wild-type littermates. Moreover, β-cell mass and the total number of islets did not differ between STZ-induced Rspo1+/+ and Rspo1-/- mice, although mice with Rspo1 deficiency had reduced β-cell apoptosis and significantly enhanced numbers of insulin-positive ductal cells suggestive of β-cell neogenesis. Furthermore, the increased β-cell regeneration observed in knockout animals appeared to be associated with a more differentiated/mature β-cell phenotype in Rspo1-/- versus Rspo1+/+ mice. Collectively, these findings indicate a role for Rspo1 as a negative regulator of in vivo β-cell neogenesis and survival in the face of STZ-induced diabetes.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/35589 |
| Date | 11 July 2013 |
| Creators | Chahal, Jasleen |
| Contributors | Brubaker, Patricia |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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