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N ‐acetyl‐GLP‐1: a DPP IV‐resistant analogue of glucagon‐like peptide‐1 (GLP‐1) with improved effects on pancreatic β‐cell‐associated gene expression
Author(s) -
Liu HuiKang,
Green Brian D.,
Gault Victor A.,
McCluskey Jane T.,
McClenaghan Neville H.,
O'Harte P. M. Finbarr,
Flatt Peter R.
Publication year - 2004
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2003.10.004
Subject(s) - glucagon like peptide 1 , glucokinase , glucagon like peptide 1 receptor , beta cell , insulin , glucagon , endocrinology , medicine , proglucagon , receptor , chemistry , dipeptidyl peptidase 4 , biology , biochemistry , diabetes mellitus , type 2 diabetes , islet , agonist
Glucagon‐like peptide‐1(7‐36)amide (GLP‐1) is a key insulinotropic hormone with the reported potential to differentiate non‐insulin secreting cells into insulin‐secreting cells. The short biological half‐life of GLP‐1 after cleavage by dipeptidylpeptidase IV (DPP IV) to GLP‐1(9‐36)amide is a major therapeutic drawback. Several GLP‐1 analogues have been developed with improved stability and insulinotropic action. In this study, the N‐terminally modified GLP‐1 analogue, N ‐acetyl‐GLP‐1, was shown to be completely resistant to DPP IV, unlike native GLP‐1, which was rapidly degraded. Furthermore, culture of pancreatic ductal ARIP cells for 72 h with N ‐acetyl‐GLP‐1 indicated a greater ability to induce pancreatic β‐cell‐associated gene expression, including insulin and glucokinase. Further investigation of the effects of stable GLP‐1 analogues on β‐cell differentiation is required to assess their potential in diabetic therapy.