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

DOI: 10.4236/jdm.2013.33017   PDF   HTML     2,391 Downloads   3,832 Views   Citations

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.

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Lai, M. , Lo, Y. and Yang, C. (2013) The effect of demethylasterriquinone B-1 on insulin secretion in rat pancreas. Journal of Diabetes Mellitus, 3, 116-121. doi: 10.4236/jdm.2013.33017.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Zhang, B.B., Salituro, G.M., Szalkowski, D., Li, Z., Zhang, Y., Royo, I., Vilella, D., Diez, M.T., Pelaez, F., Ruby, C., Kendall, R.L., Mao, X., Griffin, P., Calaycay, J., Zierath, J.R., Heck, J.V., Smith, R.G. and Moller, D.E. (1999) Discovery of a small molecule insulin mimetic with antidiabetic activity in mice. Science, 284, 974-977. doi:10.1126/science.284.5416.974
[2] Webster, N.J., Park, K. and Pirrung, M.C. (2003) Signaling effects of demethylasterriquinone B1, a selective insulin receptor modulator. Chembiochem, 4, 379-385. doi:10.1002/cbic.200200468
[3] Ding, V.D.H., Qureshi, S.A., Szalkowski, D., Zhihua, L. I., Biazzo-ashnault, D.E., XIE, D., Liu, K., Jones, A.B., Moller, D.E. and Zhang, B.B. (2002) Regulation of insulin signal transduction pathway by a small-molecule insulin receptor activator. Biochemical Journal, 367, 301-306. doi:10.1042/BJ20020708
[4] Roper, M.G., Qian, W.J., Zhang, B.B., Kulkarni, R.N., Kahn, C.R. and Kennedy, R.T. (2002) Effect of the insulin mimetic L-783, 281 on intracellular Ca2+ and insulin secretion from pancreatic beta-cells. Diabetes, 51, S43-S49. doi:10.2337/diabetes.51.2007.S43
[5] Strowski, M.Z., Li, Z., Szalkowski, D., Shen, X., Guan, X.M., Juttner, S., Moller, D.E. and Zhang, B.B. (2004) Small molecule insulin mimetic reduces hyperglycemia and obesity in a non-genetic mouse model of type 2 diabetes. Endocrinology, 145, 5259-5268. doi:10.1210/en.2004-0610
[6] Velliquette, R.A., Friedman, J.E., Shao, J., Zhang, B.B. and Ernsberger, P. (2005) Therapeutic actions of an insulin receptor activator and a novel peroxisome proliferator-activated receptor γ agonist in the spontaneously hypertensive obese rat model of metabolic syndrome X. J. Journal of Pharmacology and Experimental Therapeutics, 314, 422-430. doi:10.1124/jpet.104.080606
[7] Grodsky, G.M. and Fanska, R.E. (1975) The in vitro perfused pancreas. Methods in Enzymology, 39, 364-372. doi:10.1016/S0076-6879(75)39033-2
[8] Hale, C.N. and Randle, P.J. (1963) Immunoassay of insulin with insulin antibody precipitate. Biochemical Journal, 88, 137-146.
[9] Vlahos, C.J., Matter, W.F., Hui, K.Y. and Brown, R.F. (1994) A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). The Journal of Biological Chemistry, 269, 5241-5248.
[10] Walker, E.H., Pacold, M.E., Perisic, O., Stephens, L., Hawkins, P.T., Wymann, M.P. and Williams, R.L. (2000) Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Molecular Cell, 6, 909-919. doi:10.1016/S1097-2765(05)00089-4
[11] Salituro, G.M., Pelaez, F. and Zhang, B.B. (2001) Discovery of a small molecule insulin receptor activator. Recent Progress in Hormone Research, 56, 107-126. doi:10.1210/rp.56.1.107

  
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