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dc.contributor.authorBall, A. J.
dc.contributor.authorMcCluskey, Jane T.
dc.contributor.authorFlatt, P. R.
dc.contributor.authorMcClenaghan, N. H.
dc.date.accessioned2018-06-29T21:32:54Z
dc.date.available2018-06-29T21:32:54Z
dc.date.issued2000-04-29
dc.identifierER4509
dc.identifier.citationBall, A., McCluskey, J., Flatt, P. & McClenaghan, N. (2000) Drug-induced desensitization of insulinotropic actions of sulfonylureas., Biochemical and biophysical research communications, vol. 271, , pp. 234-9,
dc.identifier.issn0006-291X
dc.identifier.urihttp://dx.doi.org/10.1006/bbrc.2000.2609
dc.identifier.urihttps://eresearch.qmu.ac.uk/handle/20.500.12289/4509
dc.description.abstractK(ATP)-channel-dependent and K(ATP)-channel-independent insulin-releasing actions of the sulfonylurea, tolbutamide, were examined in the clonal BRIN-BD11 cell line. Tolbutamide stimulated insulin release at both nonstimulatory (1.1 mM) and stimulatory (16. 7 mM) glucose. Under depolarizing conditions (16.7 mM glucose plus 30 mM KCl) tolbutamide evoked a stepwise K(ATP) channel-independent insulinotropic response. Culture (18 h) with tolbutamide or the guanidine derivative BTS 67 582 (100 microM) markedly reduced (P < 0. 001) subsequent responsiveness to acute challenge with tolbutamide, glibenclamide, and BTS 67 582 but not the imidazoline drug, efaroxan. Conversely, 18 h culture with efaroxan reduced (P < 0.001) subsequent insulinotropic effects of efaroxan but not that of tolbutamide, glibenclamide, or BTS 67 582. Culture (18 h) with tolbutamide reduced the K(ATP) channel-independent actions of both tolbutamide and glibenclamide. Whereas culture with efaroxan exerted no effect on the K(ATP) channel-independent actions of sulfonylureas, BTS 67 582 abolished the response of tolbutamide and inhibited that of glibenclamide. These data demonstrate that prolonged exposure to tolbutamide desensitizes both K(ATP)-channel-dependent and -independent insulin-secretory actions of sulfonylureas, indicating synergistic pathways mediated by common sulfonylurea binding site(s).
dc.format.extent234-9
dc.publisherElsevier
dc.relation.ispartofBiochemical and biophysical research communications
dc.titleDrug-induced desensitization of insulinotropic actions of sulfonylureas.
dc.typearticle
dcterms.accessRightsnone
dc.description.facultysch_die
dc.description.volume271
dc.identifier.doihttp://10.1006/bbrc.2000.2609
dc.description.ispublishedpub
dc.description.eprintid4509
rioxxterms.typearticle
qmu.authorMcCluskey, Jane T.
dc.description.statuspub
dc.description.number1


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