Abstract
Exploitation of glucose-dependent insulinotropic polypeptide (GIP) is hindered by its short biological half-life and rapid renal clearance. To circumvent these problems, two novel acylated N-terminally modified GIP analogues, N-pGluGIP(LysPAL16) and N-pGluGIP(LysPAL37), were evaluated. In contrast to native GIP, both analogues were completely resistant to dipeptidyl peptidase IV degradation. In GIP-receptor transfected fibroblasts, N-pGluGIP(LysPAL16) and N-pGluGIP(LysPAL37) exhibited enhanced stimulation of cAMP production. Insulinotropic responses in clonal beta-cells were similar to native GIP. When administered together with glucose to ob/ob mice, the glycemic excursions were significantly less for both analogues and insulin responses were greater than native GIP. Extended insulinotropic and antihyperglycemic actions were also evident. These data indicate that palmitate-derivitized analogues of N-terminal pyroglutamyl GIP represent a novel class of stable, long-acting, and effective GIP analogues for potential type 2 diabetes therapy.
Publication DOI: | https://doi.org/10.1021/jm049262s |
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Divisions: | Life & Health Sciences > Biosciences Life & Health Sciences Life & Health Sciences > Applied Health Research Group |
Uncontrolled Keywords: | Organic Chemistry |
Full Text Link: | |
Related URLs: |
http://www.scop ... tnerID=8YFLogxK
(Scopus URL) |
Published Date: | 2005 |
Authors: |
Irwin, Nigel
Green, Brian D. Gault, Victor A. Greer, Brett Harriott, Patrick Bailey, Clifford J. ( ![]() Flatt, Peter R. O'Harte, Finbarr P.M. |