Complete sequences of glucagon-like peptide-1 from human and pig small intestine
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Complete sequences of glucagon-like peptide-1 from human and pig small intestine. / Orskov, C; Bersani, M; Johnsen, A H; Højrup, P; Holst, J J.
In: The Journal of Biological Chemistry, Vol. 264, No. 22, 05.08.1989, p. 12826-9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Complete sequences of glucagon-like peptide-1 from human and pig small intestine
AU - Orskov, C
AU - Bersani, M
AU - Johnsen, A H
AU - Højrup, P
AU - Holst, J J
PY - 1989/8/5
Y1 - 1989/8/5
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Amino Acids/isolation & purification
KW - Animals
KW - Chromatography, High Pressure Liquid
KW - Gas Chromatography-Mass Spectrometry
KW - Gastrointestinal Hormones/isolation & purification
KW - Glucagon-Like Peptide 1
KW - Glycosylation
KW - Humans
KW - Intestine, Small
KW - Molecular Sequence Data
KW - Peptides/isolation & purification
KW - Swine
M3 - Journal article
C2 - 2753890
VL - 264
SP - 12826
EP - 12829
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 22
ER -
ID: 194815950