Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Involvement of Ca2+/Calmodulin Kinase II (CaMK II) in Genistein-Induced Potentiation of Leucine/Glutamine-Stimulated Insulin Secretion

  • Lee, Soo-Jin (Institute for Medical Science, Ajou University School of Medicine) ;
  • Kim, Hyo-Eun (Institute for Medical Science, Ajou University School of Medicine) ;
  • Choi, Sung-E (Institute for Medical Science, Ajou University School of Medicine) ;
  • Shin, Ha-Chul (Institute for Medical Science, Ajou University School of Medicine) ;
  • Kwag, Won-Jae (Yuhan Pharmaceutical Research Center) ;
  • Lee, Byung-Kyu (Yuhan Pharmaceutical Research Center) ;
  • Cho, Ki-Woong (Department of Ocean Microbe Engineering, Anyang University) ;
  • Kang, Yup (Institute for Medical Science, Ajou University School of Medicine)
  • Received : 2009.04.16
  • Accepted : 2009.07.31
  • Published : 2009.09.30
⟨ Previous Next ⟩

Abstract

Genistein has been reported to potentiate glucose-stimulated insulin secretion (GSIS). Inhibitory activity on tyrosine kinase or activation of protein kinase A (PKA) was shown to play a role in the genistein-induced potentiation effect on GSIS. The aim of the present study was to elucidate the mechanism of genistein-induced potentiation of insulin secretion. Genistein augmented insulin secretion in INS-1 cells stimulated by various energygenerating nutrients such as glucose, pyruvate, or leucine/glutamine (Leu/Gln), but not the secretion stimulated by depolarizing agents such as KCl and tolbutamide, or $Ca^{2+}$ channel opener Bay K8644. Genistein at a concentration of $50{\mu}M$ showed a maximum potentiation effect on Leu/Gln-stimulated insulin secretion, but this was not sufficient to inhibit the activity of tyrosine kinase. Inhibitor studies as well as immunoblotting analysis demonstrated that activation of PKA was little involved in genistein-induced potentiation of Leu/Gln-stimulated insulin secretion. On the other hand, all the inhibitors of $Ca^{2+}$/calmodulin kinase II tested, significantly diminished genistein-induced potentiation. Genistein also elevated the levels of $[Ca^{2+}]_i$ and phospho-CaMK II. Furthermore, genistein augmented Leu/Gln-stimulated insulin secretion in CaMK II-overexpressing INS-1 cells. These data suggest that the activation of CaMK II played a role in genistein-induced potentiation of insulin secretion.

Keywords

Acknowledgement

Supported by : Ajou University, Gyunggi Regional Research Center (GRRC)

References

  1. Akiyama, T., Ishida, J., and Nakagawa, S. (1987). Genistein, a specific inhibitor of tyrosine-specific protein kinase. J. Biol. Chem. 262, 5592-5595
  2. Borge, P.D., Moibi, J., Greene, S.R., Trucco, M., Young, R.A., Gao, Z., and Wolf, B.A. (2002). Insulin receptor signaling and sarco/endoplasmic reticulum calcium ATPase in beta-cells. Diabetes 51, S427-S433 https://doi.org/10.2337/diabetes.51.2007.S427
  3. Bratanova-Tochkova, T.K., Cheng, H,, Daniel, S., Gunawardana, S., Liu, Y.J., Mulvaney-Musa, J., Schermerhorn, T., Straub, S.G., Yajima, H., and Sharp, G.W. (2002). Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion. Diabetes 51, S83-S90 https://doi.org/10.2337/diabetes.51.2007.S83
  4. Davies, S.P., Reddy, H., Caivano, M., and Cohen, P. (2000). Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351, 95-105 https://doi.org/10.1042/0264-6021:3510095
  5. Eto, K., Yamashita, T., Tsubamoto, Y., Terauchi, Y., Hirose, K., Kubota, N., Yamashita, S., Taka, J., Satoh, S., Sekihara, H., et al. (2002). Phosphatidylinositol 3-kinase suppresses glucosestimulated insulin secretion by affecting post-cytosolic [Ca(2+)] elevation signals Diabetes 51, 87-97 https://doi.org/10.2337/diabetes.51.1.87
  6. Henquin, J.C. (2000). Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49, 751-760
  7. Jonas, J.C., Plant, T.D., Gilon, P., Detimary, P., Nenquin, M., and Henquin, J.C. (1995). Multiple effects and stimulation of insulin secretion by the tyrosine kinase inhibitor genistein in normal mouse islets. Br. J. Pharmacol. 114, 872-880 https://doi.org/10.1111/j.1476-5381.1995.tb13285.x
  8. Kang, K., Lee, S.B., Jung, S.H., Cha, K.H., Park, W.D., Sohn, Y.C., and Nho, C.W. (2009). Tectoridin, a poor ligand of estrogen receptor alpha, exerts its estrogenic effects via an ERK-dependent pathway. Mol. Cells 27, 351-357 https://doi.org/10.1007/s10059-009-0045-8
  9. Knudsen, P., Kofod, H., Lernmark, A., and Hedeskov, C.J. (1983). L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase. Am. J. Physiol. Endocrinol. Metab. 245, E338-E346 https://doi.org/10.1152/ajpendo.1983.245.4.E338
  10. Linassier, C., Pierre, M., Le Pecq, J.B., and Pierre, J. (1990). Mechanisms of action in NIH-3T3 cells of genistein, an inhibitor of EGF receptor tyrosine kinase activity. Biochem. Pharmacol. 39, 187-193 https://doi.org/10.1016/0006-2952(90)90664-7
  11. Liu, Y.J., Cheng, H., Drought, H., MacDonald, M.J., Sharp, G.W., and Straub, S.G. (2003). Activation of the KATP channelindependent signaling pathway by the nonhydrolyzable analog of leucine, BCH. Am. J. Physiol. Endocrinol. Metab. 285, E380-E389 https://doi.org/10.1152/ajpendo.00008.2003
  12. Liu, D., Jiang, H., and Grange, R.W. (2005). Genistein activates the 3′,5′-cyclic adenosine monophosphate signaling pathway in vascular endothelial cells and protects endothelial barrier function. Endocrinology 146, 1312-1320 https://doi.org/10.1210/en.2004-1221
  13. Liu, D., Zhen, W., Yang, Z., Carter, J.D., Si, H., and Reynolds, K.A. (2006). Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a cAMP-dependent protein kinase pathway. Diabetes 55, 1043-1050 https://doi.org/10.2337/diabetes.55.04.06.db05-1089
  14. Maechler, P. (2002). Mitochondria as the conductor of metabolic signals for insulin exocytosis in pancreatic beta-cells. Cell. Mol. Life Sci. 59, 1803-1818 https://doi.org/10.1007/PL00012507
  15. Markiewicz, L., Garey, J., and Adlercreutz, H. (1993). In vitro bioassays of non-steroidal phytoestrogens. J. Steroi. Biochem. Mol. Biol. 45, 399-405 https://doi.org/10.1016/0960-0760(93)90009-L
  16. Markovits, J., Linassier, C., Fosse, P., Couprie, J., Pierre, J., Jacquemin- Sablon, A., Saucier, J.M., Le Pecq, J.B., and Larsen, A.K. (1989). Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II. Cancer Res. 49, 5111-5117
  17. Nesher, R., Anteby, E., Yedovizky, M., Warwar, N., Kaiser, N., and Cerasi, E. (2002). Beta-cell protein kinases and the dynamics of the insulin response to glucose. Diabetes 51, S68-S73 https://doi.org/10.2337/diabetes.51.2007.S68
  18. Ng, W.W., Keung, W., Xu, Y.C., Ng, K.F., Leung, G.P., Vanhoutte, P.M., Choy, P.C., and Man, R.Y. (2008). Genistein potentiates protein kinase A activity in porcine coronary artery. Mol. Cell. Biochem. 311, 37-44 https://doi.org/10.1007/s11010-007-9691-3
  19. Ohno, T., Kato, N., Ishii, C., Shimizu, M., Ito, Y., Tomono, S., and Kawazu, S. (1993). Genistein augments cyclic adenosine 3′5′- monophosphate(cAMP) accumulation and insulin release in MIN6 cells. Endocrine Res. 19, 273-285 https://doi.org/10.1080/07435809309026682
  20. Ohsugi, M., Cras-Meneur, C., Zhou, Y., Bernal-Mizrachi, E., Johnson, J.D., Luciani, D.S., Polonsky, K.S., and Permutt, M.A. (2005). Reduced expression of the insulin receptor in mouse insulinoma (MIN6) cells reveals multiple roles of insulin signaling in gene expression, proliferation, insulin content, and secretion. J. Biol. Chem. 280, 4992-5003 https://doi.org/10.1074/jbc.M411727200
  21. Persaud, S.J., Harris, T.E., Burns, C.J., and Jones, P.M. (1999) Tyrosine kinases play a permissive role in glucose-induced insulin secretion from adult rat islets. J. Mol. Endocrinol. 22, 19-28 https://doi.org/10.1677/jme.0.0220019
  22. Sorenson, R.L., Brelje, T.C., and Roth, C. (1994). Effect of tyrosine kinase inhibitors on islets of langerhans: evidence for tyrosine kinases in the regulation of insulin secretion. Endocrinology 134, 1975-1978 https://doi.org/10.1210/en.134.4.1975
  23. Straub, S.G., and Sharp, G.W. (2002). Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes Metab. Res. Rev. 18, 451-463 https://doi.org/10.1002/dmrr.329
  24. Verspohl, E.J., Tollkuhn, B., and Kloss, H. (1995). Role of tyrosine kinase in insulin release in an insulin secreting cell line (INS-1). Cell Signal. 7, 505-512 https://doi.org/10.1016/0898-6568(95)00020-P
  25. Wan, Q.F., Dong, Y., Yang, H., Lou, X., Ding, J., and Xu, T. (2004). Protein kinase activation increases insulin secretion by sensitizing the secretory machinery to Ca2+. J. Gen. Physiol. 124, 653-662 https://doi.org/10.1085/jgp.200409082
  26. Wiederkehr, A., and Wollheim, C.B. (2006). Minireview: implication of mitochondria in insulin secretion and action. Endocrinology 147, 2643-2649 https://doi.org/10.1210/en.2006-0057
  27. Zawalich, W.S., and Zawalich, K.C. (2002). Effects of glucose, exogenous insulin, and carbachol on C-peptide and insulin secretion from isolated perifused rat islets. J. Biol. Chem. 277, 26233-26237 https://doi.org/10.1074/jbc.M202291200
  28. Zawalich, W.S., Yamazaki, H., Zawalich, K.C., and Cline, G. (2004). Comparative effects of amino acids and glucose on insulin secretion from isolated rat or mouse islets. J. Endocrinol. 183, 309-319 https://doi.org/10.1677/joe.1.05832

Cited by

  1. Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function vol.4, pp.2, 2013, https://doi.org/10.1039/c2fo30199g
  2. Target guided isolation, in-vitro antidiabetic, antioxidant activity and molecular docking studies of some flavonoids from Albizzia Lebbeck Benth . bark vol.14, pp.None, 2009, https://doi.org/10.1186/1472-6882-14-155
  3. Sarm1 deficiency impairs synaptic function and leads to behavioral deficits, which can be ameliorated by an mGluR allosteric modulator vol.8, pp.None, 2009, https://doi.org/10.3389/fncel.2014.00087
  4. Nutritional Energy Stimulates NAD + Production to Promote Tankyrase-Mediated PARsylation in Insulinoma Cells vol.10, pp.4, 2015, https://doi.org/10.1371/journal.pone.0122948
  5. The Anthocyanin Delphinidin 3-Rutinoside Stimulates Glucagon-Like Peptide-1 Secretion in Murine GLUTag Cell Line via the Ca 2+ /Calmodulin-Dependent Kinase II Pathway vol.10, pp.5, 2009, https://doi.org/10.1371/journal.pone.0126157
  6. Hard-to-cook bean (Phaseolus vulgaris L.) proteins hydrolyzed by alcalase and bromelain produced bioactive peptide fractions that inhibit targets of type-2 diabetes and oxidative stress vol.76, pp.3, 2009, https://doi.org/10.1016/j.foodres.2015.07.046
  7. Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids vol.17, pp.4, 2009, https://doi.org/10.3390/ijms17040569
  8. Advances in research on the pathogenesis of depression based on signaling pathways vol.218, pp.None, 2009, https://doi.org/10.1051/e3sconf/202021803017