Abstract
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 language | English |
|---|---|
| Journal | The Journal of Biological Chemistry |
| Volume | 264 |
| Issue number | 22 |
| Pages (from-to) | 12826-9 |
| Number of pages | 4 |
| ISSN | 0021-9258 |
| Publication status | Published - 5 Aug 1989 |
Keywords
- 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