Isolation and Characterization of a 60-Residue Intestinal Peptide Structurally Related to the Pancreatic Secretory Type of Trypsin Inhibitor: Influence on Insulin Secretion

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-11, Vol.86 (21), p.8590-8594
• Main Authors: Agerberth, Birgitta, Söderling-Barros, Jane, Jörnvall, Hans, Chen, Zheng-Wang, Östenson, Claes-Göran, Efendić, Suad, Mutt, Viktor
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Disulfides; Fundamental and applied biological sciences. Psychology; Gastrointestinal Hormones - genetics; Gastrointestinal Hormones - isolation & purification; Gastrointestinal Hormones - pharmacology; Hormones; In Vitro Techniques; Insulin; Insulin - metabolism; Insulin Secretion; intestine; Intestine, Small - analysis; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Male; Molecular Sequence Data; Pancreas; pigs; Protease inhibitors; Proteins; Quaternary ammonium compounds; Rats; Rats, Inbred Strains; Sequence Homology, Nucleic Acid; Somatostatin - metabolism; Swine; Trypsin Inhibitor, Kazal Pancreatic - genetics; Trypsin inhibitors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.21.8590

We have isolated from pig intestine a 60-residue polypeptide initially identified by its inhibition of glucose-induced insulin secretion from perfused pancreas. The amino acid sequence of this porcine polypeptide was determined and found to be markedly similar to that of the pancreatic secretory trypsin inhibitor (41% residue identities). Furthermore, the disulfide arrangements of these two proteins appear identical, suggesting related overall conformations. However, the polypeptide, now named PEC-60 (peptide with N-terminal glutamic acid, C-terminal cysteine, and a total of 60 residues), was found not to inhibit trypsin. The amino acid sequence is also similar to that of a peptide recently isolated from rat bile/pancreatic juice which stimulates the release of cholecystokinin. The biological role of PEC-60 is not known, but the effect on insulin secretion and the homologies observed suggest important biological activities and interesting structural relationships.