Both amidated and nonamidated forms of glucagon-like peptide I are synthesized in the rat intestine and the pancreas

Biologically active peptides are initially synthesized in the form of protein precursors, and the peptides are liberated by post-translational processing from the precursors in a tissue-specific manner. Mammalian proglucagon, which is synthesized in the neuroendocrine L-cells of the intestine and th...

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Bibliographic Details
Published in:The Journal of biological chemistry 1990-05, Vol.265 (14), p.8001-8008
Main Authors: Mojsov, S, Kopczynski, M G, Habener, J F
Format: Article
Language:English
Subjects:
Animals
Antibody Specificity
Chromatography, Gel
Chromatography, High Pressure Liquid
Epitopes - immunology
Glucagon - biosynthesis
Glucagon - immunology
Glucagon - isolation & purification
Glucagon-Like Peptide 1
Immune Sera - immunology
Intestinal Mucosa - metabolism
Pancreas - metabolism
Peptide Fragments - biosynthesis
Peptide Fragments - immunology
Peptide Fragments - isolation & purification
Protein Precursors - biosynthesis
Protein Precursors - immunology
Protein Precursors - isolation & purification
Protein Processing, Post-Translational
Radioimmunoassay
Rats
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Summary:Biologically active peptides are initially synthesized in the form of protein precursors, and the peptides are liberated by post-translational processing from the precursors in a tissue-specific manner. Mammalian proglucagon, which is synthesized in the neuroendocrine L-cells of the intestine and the alpha-cells of the pancreas, contains within its structure the sequences of glucagon and two glucagon-like peptides (GLP-I and GLP-II) flanked at their amino and carboxyl termini by dibasic residues. Tissue-specific processing liberates different peptides in the intestine compared with the pancreas. One of these intestinal peptides, glucagon-like peptide I(7-37) (GLP-I(7-37], is one of the most potent insulin secretagogues studied to date. It contains within its carboxyl-terminal domain an arginine residue that, because of an adjacent glycine residue, may alternatively be used during post-translational processing as a site for amidation. Using a chromatographic system and radioimmunoassays that discriminate among the closely related GLP-I peptides, we find that the processing of proglucagon in the rat intestine and to a lesser extent in the rat pancreas results in the formation of at least three GLP-I peptides, of 37, 31, and 30 residues. The 30-residue peptide is in the form of an alpha-carboxyl-terminal arginine amide, a modification that is not usually found in proteins. Remarkably, the relative potencies for the stimulation of insulin secretion from the perfused rat pancreas of the nonamidated (GLP-I(7-37] and the amidated (GLP-I(7-36) amide) peptides are the same (Weir, G. C., Mojsov, S., Hendrik, G. K., and Habener, J. F. (1989) Diabetes 38, 338-342; Suzuki, S., Kawai, K., Okashir, S., Mukal, H., and Yamashita, K. (1989) Endocrinology 125, 3109-3114).
ISSN:0021-9258
1083-351X
DOI:10.1016/s0021-9258(19)39030-1