Reduction of diffusion barriers in isolated rat islets improves survival, but not insulin secretion or transplantation outcome

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dc.contributor.authorWilliams, S. Janette
dc.contributor.authorHuang, Han-Hung
dc.contributor.authorKover, Karen
dc.contributor.authorMoore, Wayne V
dc.contributor.authorBerkland, Cory
dc.contributor.authorSingh, Milind
dc.contributor.authorSmirnova, Irina S.
dc.contributor.authorMacGregor, Ronal
dc.contributor.authorStehno-Bittel, Lisa
dc.date.accessioned2024-02-23T16:28:32Z
dc.date.available2024-02-23T16:28:32Z
dc.date.issued2010-04-01
dc.description.abstractFor people with type 1 diabetes and severe hypoglycemic unawareness, islet transplants offer hope for improving the quality of life. However, islet cell death occurs quickly during or after transplantation, requiring large quantities of islets per transplant. The purpose of this study was to determine whether poor function demonstrated in large islets was a result of diffusion barriers and if removing those barriers could improve function and transplantation outcomes. Islets were isolated from male DA rats and measured for cell viability, islet survival, glucose diffusion and insulin secretion. Modeling of diffusion barriers was completed using dynamic partial differential equations for a sphere. Core cell death occurred in 100% of the large islets (diameter > 150 μm), resulting in poor survival within 7 days after isolation. In contrast, small islets (diameter < 100 μm) exhibited good survival rates in culture (91%). Glucose diffusion into islets was tracked with 2-NBDG; 4.2 μm/min in small islets and 2.8 μm/min in large islets. 2-NBDG never permeated to the core cells of islets larger than 150μm diameter. Reducing the diffusion barrier in large islets improved their immediate and long-term viability in culture. However, reduction of the diffusion barrier in large islets failed to improve their inferior in vitro insulin secretion compared to small islets, and did not return glucose control to diabetic animals following transplantation. Thus, diffusion barriers lead to low viability and poor survival for large islets, but are not solely responsible for the inferior insulin secretion or poor transplantation outcomes of large versus small islets.
dc.identifier.citationThis is the published version of an article that is available at https://doi.org/10.4161/org.6.2.10373. Recommended citation: Williams, S. J., Huang, H.-H., Kover, K., Moore, W. V., Berkland, C., Singh, M., Smirnova, I. S., MacGregor, R., & Stehno-Bittel, L. (2010). Reduction of diffusion barriers in isolated rat islets improves survival, but not insulin secretion or transplantation outcome. Organogenesis, 6(2), 115–124. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.
dc.identifier.urihttps://doi.org/10.4161/org.6.2.10373
dc.identifier.urihttps://hdl.handle.net/11274/15784
dc.language.isoen_US
dc.rights.licenseCC BY-NC 3.0
dc.titleReduction of diffusion barriers in isolated rat islets improves survival, but not insulin secretion or transplantation outcome
dc.typeArticle

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