DPP IV resistance and insulin releasing activity of a novel di-substituted analogue of glucose-dependent insulinotropic polypeptide, (Ser2–Asp13)GIP

Structure–function studies suggest that preservation of the N-terminus and secondary structure of glucose-dependent insulinotropic polypeptide (GIP) is important for biological activity. Therefore, a novel di-substituted analogue of GIP, (Ser2–Asp13)GIP, containing a negatively charged Asp residue i...

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Bibliographic Details
Published in:Cell biology international 2003-01, Vol.27 (1), p.41-46
Main Authors: Gault, V.A., Irwin, N., Harriott, P., Flatt, P.R., O’Harte, F.P.M.
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Animals
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - metabolism
Dipeptidylpeptidase IV
Gastric Inhibitory Polypeptide - chemical synthesis
Gastric Inhibitory Polypeptide - metabolism
GIP analogue
Glucose-dependent insulinotropic polypeptide
Insulin - metabolism
Insulin Secretion
Insulinoma
Islets of Langerhans - cytology
Islets of Langerhans - enzymology
Islets of Langerhans - metabolism
Protein Structure, Secondary
Rats
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Tumor Cells, Cultured
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Summary:Structure–function studies suggest that preservation of the N-terminus and secondary structure of glucose-dependent insulinotropic polypeptide (GIP) is important for biological activity. Therefore, a novel di-substituted analogue of GIP, (Ser2–Asp13)GIP, containing a negatively charged Asp residue in place of an Ala in position 13, was synthesised and evaluated for in vitro biological activity. Incubation with dipeptidyl peptidase IV (DPP IV) showed the half-lives of GIP and (Ser2–Asp13)GIP to be 2.3 and >4h, respectively. Insulin releasing studies in clonal pancreatic BRIN-BD11 cells demonstrated that (Ser2–Asp13)GIP (10−12to 10−7mol/l) was significantly less potent (60–90%; P
ISSN:1065-6995
1095-8355
DOI:10.1016/S1065-6995(02)00255-X