Show simple item record

dc.contributor.authorGreen, B. D.
dc.contributor.authorLiu, H. K.
dc.contributor.authorMcCluskey, Jane T.
dc.contributor.authorDuffy, N. A.
dc.contributor.authorO'Harte, F. P. M.
dc.contributor.authorMcClenaghan, N. H.
dc.contributor.authorFlatt, P. R.
dc.date.accessioned2018-06-29T21:33:59Z
dc.date.available2018-06-29T21:33:59Z
dc.date.issued2005-09
dc.identifierER4495
dc.identifier.citationGreen, B., Liu, H., McCluskey, J., Duffy, N., O''Harte, F., McClenaghan, N. & Flatt, P. (2005) Function of a long-term, GLP-1-treated, insulin-secreting cell line is improved by preventing DPP IV-mediated degradation of GLP-1, Diabetes, Obesity and Metabolism, vol. 7, , pp. 563-569,
dc.identifier.issn1462-8902
dc.identifier.urihttp://doi.org/10.1111/j.1463-1326.2004.00430.x
dc.identifier.urihttps://eresearch.qmu.ac.uk/handle/20.500.12289/4495
dc.description.abstractGlucagon-like peptide-1 (GLP-1) is an important insulinotropic hormone with potential in the treatment of type 2 diabetes. However, the short biological half-life of the peptide after cleavage by dipeptidylpeptidase IV (DPP IV) is a major limitation. Inhibition of DPP IV activity and the development of resistant GLP-1 analogues is the subject of ongoing research. In this study, we determined cell growth, insulin content, insulin accumulation and insulin secretory function of a insulin-secreting cell line cultured for 3 days with either GLP-1, GLP-1 plus the DPP IV inhibitor diprotin A (DPA) or stable N-acetyl-GLP-1. Native GLP-1 was rapidly degraded by DPP IV during culture with accumulation of the inactive metabolite GLP-1(9-36)amide. Inclusion of DPA or use of the DPP IV-resistant analogue, N-acetyl-GLP-1, improved cellular function compared to exposure to GLP-1 alone. Most notably, basal and accumulated insulin secretion was enhanced, and glucose responsiveness was improved. However, prolonged GLP-1 treatment resulted in GLP-1 receptor desensitization regardless of DPP IV status. The results indicate that prevention of DPP IV action is necessary for beneficial effects of GLP-1 on pancreatic beta cells and that prolonged exposure to GLP-1(9-36)amide may be detrimental to insulin secretory function. These observations also support the ongoing development of DPP-IV-resistant forms of GLP-1, such as N-acetyl-GLP-1.
dc.format.extent563-569
dc.publisherWiley
dc.relation.ispartofDiabetes, Obesity and Metabolism
dc.titleFunction of a long-term, GLP-1-treated, insulin-secreting cell line is improved by preventing DPP IV-mediated degradation of GLP-1
dc.typearticle
dcterms.accessRightsnone
dc.description.facultysch_die
dc.description.volume7
dc.identifier.doihttp://doi:10.1111/j.1463-1326.2004.00430.x
dc.description.ispublishedpub
dc.description.eprintid4495
rioxxterms.typearticle
qmu.authorMcCluskey, Jane T.
dc.description.statuspub
dc.description.number5


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record