Abstract
Glucagon-like peptide-1 is a gastrointestinal hormone that strongly stimulates insulin release via specific receptors on the pancreatic beta-cell. To characterize the side-chain groups required for interaction of glucagon-like peptide-1 with its receptor, we performed binding studies with alanine-substituted glucagon-like peptide-1 analogues on RINm5F insulinoma cells. The binding affinity and biological activity of glucagon-like peptide-1 have been found to be sensitive to alanine exchanges in the N-terminal positions 1, 4, 6 and the C-terminal positions 22 and 23. Alanine substitutions at positions 5, 8, 10-12, 14, 16-21 and 25-30 do not change receptor affinity. These findings could be exploited to design glucagon-like peptide-1 agonists and probably antagonists for further physiological studies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Binding, Competitive
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Cyclic AMP / biosynthesis
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Glucagon / chemistry*
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Glucagon / genetics
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Glucagon / metabolism*
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Glucagon-Like Peptide 1
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Glucagon-Like Peptide-1 Receptor
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Insulinoma / metabolism
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Kinetics
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Molecular Sequence Data
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Pancreatic Neoplasms / metabolism
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Peptide Fragments / chemistry*
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Peptide Fragments / genetics
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Peptide Fragments / metabolism*
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Protein Precursors / chemistry*
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Protein Precursors / genetics
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Protein Precursors / metabolism*
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Rats
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Receptors, Cell Surface / metabolism
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Receptors, Glucagon*
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Structure-Activity Relationship
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Tumor Cells, Cultured / metabolism
Substances
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Glp1r protein, rat
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Glucagon-Like Peptide-1 Receptor
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Peptide Fragments
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Protein Precursors
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Receptors, Cell Surface
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Receptors, Glucagon
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Glucagon-Like Peptide 1
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Glucagon
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Cyclic AMP