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dc.contributor.authorGuo-Parke, H.
dc.contributor.authorMcCluskey, Jane T.
dc.contributor.authorKelly, C.
dc.contributor.authorHamid, M.
dc.contributor.authorMcClenaghan, N. H.
dc.contributor.authorFlatt, P. R.
dc.date.accessioned2018-06-29T21:34:26Z
dc.date.available2018-06-29T21:34:26Z
dc.date.issued2012-09-01
dc.identifierER4485
dc.identifier.citationGuo-Parke, H., McCluskey, J., Kelly, C., Hamid, M., McClenaghan, N. & Flatt, P. (2012) Configuration of electrofusion-derived human insulin-secreting cell line as pseudoislets enhances functionality and therapeutic utility, Journal of Endocrinology, vol. 214, , pp. 257-265,
dc.identifier.issn0022-0795
dc.identifier.urihttp://joe.endocrinology-journals.org/content/214/3/257.long
dc.identifier.urihttps://eresearch.qmu.ac.uk/handle/20.500.12289/4485
dc.description.abstractFormation of pseudoislets from rodent cell lines has provided a particularly useful model to study homotypic islet cell interactions and insulin secretion. This study aimed to extend this research to generate and characterize, for the first time, functional human pseudoislets comprising the recently described electrofusion-derived insulin-secreting 1.1B4 human _-cell line. Structural pseudoislets formed readily over 3-7 days in culture using ultra-low-attachment plastic, attaining a static size of 100-200 _m in diameter, corresponding to ~6000 _ cells. This was achieved by decreases in cell proliferation and integrity as assessed by BrdU ELISA, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, and lactate dehydrogenase assays. Insulin content was comparable between monolayers and pseudoislets. However, pseudoislet formation enhanced insulin secretion by 17- to 125-fold in response to acute stimulation with glucose, amino acids, incretin hormones, or drugs compared with equivalent cell monolayers. Western blot and RT-PCR showed expression of key genes involved in cell communication and the stimulus-secretion pathway. Expression of E-Cadherin and connexin 36 and 43 was greatly enhanced in pseudoislets with no appreciable connexin 43 protein expression in monolayers. Comparable levels of insulin, glucokinase, and GLUT1 were found in both cell populations. The improved secretory function of human 1.1B4 cell pseudoislets over monolayers results from improved cellular interactions mediated through gap junction communication. Pseudoislets comprising engineered electrofusion-derived human _ cells provide an attractive model for islet research and drug testing as well as offering novel therapeutic application through transplantation.
dc.format.extent257-265
dc.relation.ispartofJournal of Endocrinology
dc.titleConfiguration of electrofusion-derived human insulin-secreting cell line as pseudoislets enhances functionality and therapeutic utility
dc.typearticle
dcterms.accessRightsnone
dc.description.facultysch_die
dc.description.volume214
dc.identifier.doihttp://doi:10.1530/JOE-12-0188
dc.description.ispublishedpub
dc.description.eprintid4485
rioxxterms.typearticle
qmu.authorMcCluskey, Jane T.
dc.description.statuspub
dc.description.number3


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