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    Function of a long-term, GLP-1-treated, insulin-secreting cell line is improved by preventing DPP IV-mediated degradation of GLP-1

    Date
    2005-09
    Author
    Green, B. D.
    Liu, H. K.
    McCluskey, Jane T.
    Duffy, N. A.
    O'Harte, F. P. M.
    McClenaghan, N. H.
    Flatt, P. R.
    Metadata
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    Citation
    Green, 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,
    Abstract
    Glucagon-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.
    Official URL
    http://doi.org/10.1111/j.1463-1326.2004.00430.x
    URI
    https://eresearch.qmu.ac.uk/handle/20.500.12289/4495
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    • Dietetics, Nutrition and Biological Sciences

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