The effect of demethylasterriquinone B-1 on insulin secretion in rat pancreas

Copyright © 2013 Min-Chuan Lai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A small nonpeptidyl compoud extracted from Pseudomassaria sp. was found to induce the activity of human insulin receptor tyrosine kinase in vitro. The compound was identified as demethylasterriquinone B-1 (DMAQ-B1). DMAQ-B1 also induced an increase in [Ca2+]i and in-sulin secretion in mice pancreatic beta-cells at low glucose (3 mM) concentration via insulin receptor substrate-1/phosphatidylinositol-3-kinase (PI3 kinase) pathway. By using rat pan-creatic perfusion technique, we found that 10 μM DMAQ-B1 directly stimulated insulin secretion up to 240 % in normal rat pancreas. In the dosage from 1 to 20 μM, DMAQ-B1 stimulated insulin secretion in a dose dependent manner. Fur-thermore, DMAQ-B1 enhanced glucose-induced insulin secretion by 17.6 % (first stage) and 19.0% (second stage), respectively. The PI3 kinase in-hibitors, LY 294002 (3.9 μM) or wortmannin (100 nM), inhibited DMAQ-B1-induced insulin secre-tion by 46.3 % and 57.4%, respectively. LY 294002 or wortmannin also inhibited DMAQ-B1 with 10 mM glucose-induced insulin secretion by 70.3% and 79.0%, respectively. All the results sug-gested that DMAQ-B1 directly stimulated insulin secretion and enhanced glucose-induced insu-lin secretion. The effect of DMAQ-B1 may medi-ate through the activation of PI3 kinase pathway to stimulate insulin secretion in normal rat pan-creas