Complete sequences of glucagon-like peptide-1 from human and pig small intestine

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C Orskov, M Bersani, A H Johnsen, P Højrup, J J Holst

In the small intestine, proglucagon is processed into the previously characterized peptide "glicentin" (proglucagon (PG) 1-69) and two smaller peptides showing about 50% homology with glucagon: glucagon-like peptide-1 and -2. It was assumed that the sites of post-translational cleavage in the small intestine of the proglucagon precursor were determined by pairs of basic amino acid residues flanking the two peptides. Earlier studies have shown that synthetic glucagon-like peptide-1 (GLP-1) synthesized according to the proposed structure (proglucagon 71-108 or because residue 108 is Gly, 72-107 amide) had no physiological effects, whereas a truncated from of GLP-1, corresponding to proglucagon 78-107 amide, strongly stimulated insulin secretion and depressed glucagon secretion. To determine the amino acid sequence of the naturally occurring peptide we isolated GLP-1 from human small intestine by hydrophobic, gel permeation, and reverse-phase high performance liquid chromatography. By analysis of composition and sequence it was determined that the peptide corresponded to PG 78-107. By mass spectrometry the molecular mass was determined to be 3295, corresponding to PG 78-107 amide. Furthermore, mass spectrometry of the methyl-esterified peptide showed an increase in mass compatible with the presence of alpha-carboxyl amidation. Thus, the gut-derived insulinotrophic hormone GLP-1 is shown to be PG 78-107 amide.

Original languageEnglish
JournalThe Journal of Biological Chemistry
Volume264
Issue number22
Pages (from-to)12826-9
Number of pages4
ISSN0021-9258
Publication statusPublished - 5 Aug 1989

    Research areas

  • Amino Acid Sequence, Amino Acids/isolation & purification, Animals, Chromatography, High Pressure Liquid, Gas Chromatography-Mass Spectrometry, Gastrointestinal Hormones/isolation & purification, Glucagon-Like Peptide 1, Glycosylation, Humans, Intestine, Small, Molecular Sequence Data, Peptides/isolation & purification, Swine

ID: 194815950