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dc.contributor.authorHostelley, Timothy L
dc.contributor.authorNesmith, Jessica E
dc.contributor.authorLarkin, Emily
dc.contributor.authorJones, Amanda
dc.contributor.authorBoyes, Daniel
dc.contributor.authorLeitch, Carmen C
dc.contributor.authorFontaine, Magali
dc.contributor.authorZaghloul, Norann A
dc.date.accessioned2021-06-17T13:18:15Z
dc.date.available2021-06-17T13:18:15Z
dc.date.issued2021-06-14
dc.identifier.urihttp://hdl.handle.net/10713/16038
dc.description.abstractPancreatic β-cells are a critical cell type in the pathology of diabetes. Models of genetic syndromes featuring diabetes can provide novel mechanistic insights into regulation of β-cells in the context of disease. We previously examined β-cell mass in models of two ciliopathies, Alström Syndrome (AS) and Bardet-Biedl Syndrome (BBS), which are similar in the presence of metabolic phenotypes, including obesity, but exhibit strikingly different rates of diabetes. Zebrafish models of these disorders show deficient β-cells with diabetes in AS models and an increased β-cells absent diabetes in BBS models, indicating β-cell generation or maintenance that correlates with disease prevalence. Using transcriptome analyses, differential expression of several exocrine pancreas proteases with directionality that was consistent with β-cell numbers were identified. Based on these lines of evidence, we hypothesized that pancreatic proteases directly impact β-cells. In the present study, we examined this possibility and found that pancreatic protease genes contribute to proper maintenance of normal β-cell numbers, proliferation in larval zebrafish, and regulation of AS and BBS β-cell phenotypes. Our data suggest that these proteins can be taken up directly by cultured β-cells and ex vivo murine islets, inducing proliferation in both. Endogenous uptake of pancreatic proteases by β-cells was confirmed in vivo using transgenic zebrafish and in intact murine pancreata. Taken together, these findings support a novel proliferative signaling role for exocrine pancreas proteases through interaction with endocrine β-cells.en_US
dc.description.urihttps://doi.org/10.1242/bio.046839en_US
dc.language.isoenen_US
dc.publisherThe Company of Biologists Ltd.en_US
dc.relation.ispartofBiology Openen_US
dc.rights© 2021. Published by The Company of Biologists Ltd.en_US
dc.subjectCiliopathiesen_US
dc.subjectDiabetesen_US
dc.subjectZebrafishen_US
dc.subjectβ-cellsen_US
dc.titleExocrine pancreas proteases regulate β-cell proliferation in zebrafish ciliopathy models and in murine systemsen_US
dc.typeArticleen_US
dc.identifier.doi10.1242/bio.046839
dc.identifier.pmid34125181
dc.source.volume10
dc.source.issue6
dc.source.countryEngland


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