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

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DOI: 10.4236/jdm.2013.33017    2,306 Downloads   3,684 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.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

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.

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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