Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion

Abstract

In mammalian tissues the C-terminal amide structure has been found to occur only in neuroactive or hormonally-active peptides. About half known neuropeptide and peptide hormones have this unique chemical feature. Using a chemical detection method, a search for previously unknown peptides that possess the C-terminal amide structure in extracts of brain and intestine was carried out and a number of novel neuropeptides and hormonal peptides, designated neuropeptide Y, PHI, peptide YY, galanin and neuropeptide K were isolated. We recently performed a similar search in porcine pancreas and found a high concentration of a peptide having a glycine amide at its C-terminus. Here we report the isolation, primary structure and biological activity of this novel peptide. The 49-residue peptide strongly inhibits glucose-induced insulin release from the isolated perfused pancreas and was therefore named pancreastatin. It may be important in the regulation of insulin secretion and in the pathogenesis and treatment of diabetes mellitus.

Sorting and processing of secretory proteins

“…Although their biological function is not yet well established, it has been suggested that they may play a central role in facilitating protein sorting to the regulated pathway as well as serving as precursors for biologically active peptides (i.e. the generation of pancreastatin by proteolytic cleavage of chromogranin A) [143,144]. In vitro, secretogranin II has been shown to aggregate and precipitate when the pH was lowered to 5.2 and the Ca21 concentration raised to lOmM [104].…”

Beta cell chromogranin B is partially segregated in distinct granules and can be released separately from insulin in response to stimulation

“…Based on intracellular distribution studies [7,8] and on data obtained in other cell lines (AtT20 and PC12), these granins are believed to play important roles both in the sorting, packaging and processing of secretion products [11][12][13][14], and in the storage of Ca 2+ within SG lumina [15]. Moreover chromogranin A and/or peptides derived from its processing have been reported to play autocrine, paracrine and endocrine functions upon discharge [16][17][18][19], while CgB has been shown to induce an autocrine inhibition of insulin release from beta cells [20]. However, the functional significance of the latter process in the intact animal remains unclear.…”

Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway

“…3). These are (i) the vasostatin/fl-granin peptides, comprising the N-terminal 113 amino acids (flgranin/vasostatin II) of CGA and in some tissues (except in rat) a shorter N-terminal 76-amino acid polypeptide (vasostatin I) [91,103,104], (ii) pancreastatin [21,105], (iii) WE-14 [86,106,107] and (iv) the parastatin/GE-25 peptides [88,108,109]. Each of the peptides above have been demonstrated to exist in endocrine tissues by extraction, isolation, purification and peptide sequencing.…”