N-acetyl-GLP-1: a DPP IV-resistant analogue of glucagon-like peptide-1 (GLP-1) with improved effects on pancreatic beta-cell-associated gene expression.
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 beta-cell-associated gene expression, including insulin and glucokinase. Further investigation of the effects of stable GLP-1 analogues on beta-cell differentiation is required to assess their potential in diabetic therapy.
Liu
Hui-Kang
HK
School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, UK.
Green
Brian D
BD
Gault
Victor A
VA
McCluskey
Jane T
JT
McClenaghan
Neville H
NH
O'Harte
Finbarr P M
FP
Flatt
Peter R
PR
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D005934:Glucagon / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010183:Pancreatic Ducts / Q000166:cytology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D010446:Peptide Fragments; C485578:glucagon-like peptide-1 (7-36)amide, N-acetyl-; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon