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

Cell Biol Int. 2004;28(1):69-73. doi: 10.1016/j.cellbi.2003.10.004.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation
  • Cell Line, Tumor
  • Gene Expression / drug effects
  • Glucagon / analogs & derivatives*
  • Glucagon / chemistry
  • Glucagon / genetics
  • Glucagon / pharmacology*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism*
  • Molecular Sequence Data
  • Pancreatic Ducts / cytology
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Rats

Substances

  • Peptide Fragments
  • glucagon-like peptide-1 (7-36)amide, N-acetyl-
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon