TITLE:
The effect of demethylasterriquinone B-1 on insulin secretion in rat pancreas
AUTHORS:
Min-Chuan Lai, Yu-Shan Lo, Chi Yang
KEYWORDS:
DMAQ-B1; Insulin Secretion; PI3 Kinase; Tyrosine Kinase; Wortmannin
JOURNAL NAME:
Journal of Diabetes Mellitus,
Vol.3 No.3,
July
22,
2013
ABSTRACT:
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 insulin 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 pancreatic 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. Furthermore, DMAQ-B1 enhanced glucose-induced insulin secretion by 17.6% (first stage) and 19.0% (second stage), respectively. The PI3 kinase inhibitors, LY 294002 (3.9 μM) or
wortmannin (100 nM), inhibited DMAQ-B1-induced insulin secretion by 46.3% and
57.4%, respectively. LY 294002 or wortmannin also inhibited DMAQ-B1 with10 mMglucose-induced insulin secretion by
70.3% and 79.0%, respectively. All the results suggested that DMAQ-B1 directly
stimulated insulin secretion and enhanced glucose-induced insulin secretion. The
effect of DMAQ-B1 may mediate through the activation of PI3 kinase pathway to
stimulate insulin secretion in normal rat pancreas.