According to the CDC, the prevalence of diabetes has increased from 3.3% in 2004 to over 10.1% by 2019 (Prevalence of Diagnosed Diabetes). The United States Department of Agriculture (USDA) recommends that total fat intake should be between 20 - 35% of the total calories an individual consumes in a day and yet the Center for Disease Control and Prevention (CDC) reports that on average, total fat consumption makes up 35.8% of a person’s diet (Dietary guidelines, 2020 & CDC, 2021 respectively). According to Parrish, “dietary fat does not have an immediate effect on blood sugar levels, but consuming a meal high in fat can slow digestion and make it more difficult for insulin to work” (Parrish, 2015). Chronic diabetes can result in hypocontractility of the bladder. Contractility of the bladder is controlled by a multitude of receptors, ligands, and kinases. One receptor our group feels contributes is neuropilin 2. Our group has reported expression of neuropilin 2 in the smooth muscle of the bladder and has shown that expression induces cytoskeleton relaxation. Thus, it is thought that if neuropilin 2 expression is reduced, that potentially that hypocontractility of the bladder can be attenuated. In an in vivo model of diabetes using mice on a high fat diet for 5 months, we observed minimal changes in bladder histology, and variable Nrp2 expression. In silico analysis of data from in vivo and in vitro models of diabetes identified Nrp2 transcriptional induction compared to controls and a connection with multiple differentially expressed genes in the Nrp2 signaling pathway linked with biological processes related to a diabetic pathological state. An in vitro model of diabetes which subjected rat bladder contractile cells to high glucose identified significant cytoskeletal changes, increases in Nrp2 expression, and decreased contractility. Knock-down of Nrp2 using siRNA resulted in increased contractility of smooth muscle cells on collagen gels. These data suggest that Nrp2 signaling is altered under diabetic conditions and could be targeted to attenuate diabetes induced bladder hypocontractility. / 2025-07-06T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/46426 |
| Date | 06 July 2023 |
| Creators | King, Natalie |
| Contributors | Bragdon, Beth, Adam, Rosalyn |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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