Inhibitory effect of ODN, a naturally occurring processing product of diazepam binding inhibitor, on secretagogues-induced insulin secretion.

Abstract

Diazepam binding inhibitor (DBI1-86) is a peptide that is present in large amounts in the intestine and pancreas and which inhibits glucose-stimulated insulin release from both perfused pancreas and isolated islets in low nanomolar concentrations. Here, DBI33-50 (also known as ODN, octadecaneuropeptide), one of the naturally occurring processing products of DBI1-86, and certain synthetic modified derivatives, have been shown to inhibit glucose and glibenclamide-stimulated insulin secretion from isolated rat islets and glibenclamide-stimulated insulin secretion from hamster-insulinoma (HIT-T15) beta-cell line. DBI17-50 (TTN; triakontatetraneuropeptide), another prominent processing product of DBI, had no effect. The 50% inhibitory concentration (IC50) for the effect of ODN on insulin secretion induced by 8.3 of 16.7 mM glucose was approximately the same: 5 to 6 nM. Moreover, ODN inhibited insulin release induced by 0.01 or 1 microM glibenclamide with a similar IC50 (8 to 10 nM) in both isolated pancreatic islets and in HIT-T15 beta-cells. At concentration up to 1 microM, ODN had no effect on insulin secretion induced by PACAP (pituitary adenylate cyclase polypeptide), BAYK 8644 (methyl-(1,4-dihydro-2,6-dimethyl-3-nitro-4,2-trifluoromethylphenyl) pyridine-5-carboxylate), and only marginally it affected IBMX-(isobutylmethylxanthine) induced insulin secretion. This indicates that ODN does not act directly on ATP-regulated K+ channels, voltage dependent Ca2+ channels or cAMP production. In contrast, ODN inhibited insulin secretion induced by sodium nitroprussiate in a manner that is independent from the presence of extracellular Ca2+. These results suggest that ODN or ODN-like peptide fragments of DBI, may inhibit glucose or glibenclamide-induced insulin secretion via a signaling pathway that regulate the cytoplasmic free Ca2+ concentration.

• Authors: P De Stefanis, F Impagnatiello, A Berkovich, A Guidotti
• Journal: Regulatory peptides (Regul Pept) Vol. 56 Issue 2-3 Pg. 153-65 (Apr 14 1995) ISSN: 0167-0115 [Print] Netherlands
• PMID: 7544471 (Publication Type: Journal Article)

Chemical References

• Diazepam Binding Inhibitor
• Insulin
• Ion Channels
• Neuropeptides
• Peptide Fragments
• diazepam binding inhibitor (33-50)
• Nitroprusside
• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
• Cyclic AMP
• Glucose
• Glyburide
• Calcium
• 1-Methyl-3-isobutylxanthine

Topics

• 1-Methyl-3-isobutylxanthine (pharmacology)
• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester (pharmacology)
• Amino Acid Sequence
• Animals
• Calcium (metabolism)
• Cricetinae
• Cyclic AMP (metabolism)
• Diazepam Binding Inhibitor
• Dose-Response Relationship, Drug
• Glucose (pharmacology)
• Glyburide (pharmacology)
• In Vitro Techniques
• Insulin (metabolism)
• Insulin Secretion
• Insulinoma
• Ion Channels (metabolism)
• Islets of Langerhans (metabolism)
• Male
• Molecular Sequence Data
• Neuropeptides (metabolism, pharmacology)
• Nitroprusside (pharmacology)
• Peptide Fragments
• Rats
• Time Factors
• Tumor Cells, Cultured