Cyclic nucleotide phosphodiesterase 3B is connected to osteopontin and protein kinase CK2 in pancreatic β-cells

Emilia Heimann, Amitabh Sharma, Nalini Raghavachari, Vincent C. Manganiello, Lena Stenson, Eva Degerman

Center for Complex Network Research (CCNR), Department of Physics, Northeastern University, Boston, USA.
Department of Experimental Medical Science, Division for Diabetes, Metabolism and Endocrinology, Lund University, Lund, Sweden.
DNA Sequencing and Genomics Core, Genetics and Development Biology Center.
Pulmonary/Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, USA.

DOI: 10.4236/jbise.2013.65A011                

Abstract

Islets from RIP-PDE3B mice, exhibiting β-cell specific overexpression of the cAMP/cGMP-degrading enzyme phosphodiesterase 3B (PDE3B) and dysregulated insulin secretion, were subjected to microarray analysis. We show that osteopontin (OPN) mRNA is increased in a dose-dependent manner in islets from RIP-PDE3B mice, as compared to wild-type islets. In addition, in silico analysis shows that PDE3B and OPN are interacting. Furthermore, OPN interacts with protein kinase CK2 ina distinct submodule of the protein-protein interaction network. We studied PDE3B and OPN proteins and, in some cases, also PDE1B and PDE4C, under conditions of relevance for insulin secretion. In the presence of forskolin, PDE inhibitors, insulin, or a protein kinase CK2 inhibitor, similar alterations in protein levels of PDE3B and OPN are shown. In summary, results from using a number of strategies demonstrate a connection between PDE3B and OPNas well as a role for protein kinase CK2 inpancreatic β-cells.

Keywords

Diabetes Mellitus; Pancreatic Islets; β-Cells; cAMP; Cyclic Nucleotide Phosphodiesterases; PDE; Osteopontin; Protein Kinase CK2

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Dyachok, O., et al. (2008) Glucose-induced cyclic AMP oscillations regulate pulsatile insulin secretion. Cell Metabolism, 8, 26-37. doi:10.1016/j.cmet.2008.06.003
[2]	Straub, S.G. and Sharp, G.W. (2002) Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes/Metabolism Research and Reviews, 18, 451-463. doi:10.1002/dmrr.329
[3]	Furman, B., Ong, W.K. and Pyne, N.J. (2010) Cyclic AMP signaling in pancreatic islets. Advances in Experimental Medicine and Biology, 654, 281-304. doi:10.1007/978-90-481-3271-3_13
[4]	Pyne, N.J. and Furman, B.L. (2003) Cyclic nucleotide phosphodiesterases in pancreatic islets. Diabetologia, 46, 1179-1189. doi:10.1007/s00125-003-1176-7
[5]	Conti, M. and Beavo, J. (2007) Biochemistry and physiology of cyclic nucleotide phosphodiesterases: Essential components in cyclic nucleotide signaling. Annual Review of Biochemistry, 76, 481-511. doi:10.1146/annurev.biochem.76.060305.150444
[6]	Sharma, R.K., et al. (2006) Regulation of calmodulinstimulated cyclic nucleotide phosphodiesterase (PDE1): Review. International Journal of Molecular Medicine, 18, 95-105.
[7]	Shafiee-Nick, R., Pyne, N.J. and Furman, B.L. (1995) Effects of type-selective phosphodiesterase inhibitors on glucose-induced insulin secretion and islet phosphodiesterase activity. British Journal of Pharmacology, 115, 1486-1192. doi:10.1111/j.1476-5381.1995.tb16641.x
[8]	El-Metwally, M., et al. (1997) The effect of selective phosphodiesterase inhibitors on plasma insulin concentrations and insulin secretion in vitro in the rat. European Journal of Pharmacology, 324, 227-232. doi:10.1016/S0014-2999(97)00076-9
[9]	Han, P., et al. (1999) The calcium/calmodulin-dependent phosphodiesterase PDE1C down-regulates glucose-induced insulin secretion. The Journal of Biological Chemistry, 274, 22337-22344. doi:10.1074/jbc.274.32.22337
[10]	Zhao, A.Z., et al. (1997) Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B. Proceedings of the National Academy of Sciences of the United States of America, 94, 3223-3228. doi:10.1073/pnas.94.7.3223
[11]	Walz, H.A., et al. (2006) Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B. Journal of Endocrinology, 189, 629641. doi:10.1677/joe.1.06522
[12]	Walz, H.A., et al. (2007) Beta-cell PDE3B regulates Ca2+-stimulated exocytosis of insulin. Cell Signal, 19, 1505-1513. doi:10.1016/j.cellsig.2007.01.030
[13]	Waddleton, D., et al. (2008) Phosphodiesterase 3 and 4 comprise the major cAMP metabolizing enzymes responsible for insulin secretion in INS-1 (832/13) cells and rat islets. Biochemical Pharmacology, 76, 884-893. doi:10.1016/j.bcp.2008.07.025
[14]	Ahmad, M., et al. (2000) Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin secreting cell line BRIN-BD11. British Journal of Pharmacology, 129, 12281234. doi:10.1038/sj.bjp.0703165
[15]	Harndahl, L., et al. (2004) Beta-cell-targeted overexpression of phosphodiesterase 3B in mice causes impaired insulin secretion, glucose intolerance, and deranged islet morphology. The Journal of Biological Chemistry, 279, 15214-15222. doi:10.1074/jbc.M308952200
[16]	Gong, Q., et al. (2009) Expression and regulation of osteopontin in type 1 diabetes. Islets, 1, 34-41. doi:10.4161/isl.1.1.8629
[17]	Chen, Y., Bal, B.S. and Gorski, J.P. (1992) Calcium and collagen binding properties of osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 from bone. The Journal of Biological Chemistry, 267, 24871-8.
[18]	Takemoto, M., et al. (2000) Enhanced expression of osteopontin in human diabetic artery and analysis of its functional role in accelerated atherogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 624-628. doi:10.1161/01.ATV.20.3.624
[19]	Katakam, A.K., et al. (2005) Streptozotocin (STZ) mediates acute upregulation of serum and pancreatic osteopontin (OPN): A novel islet-protective effect of OPN through inhibition of STZ-induced nitric oxide production. Journal of Endocrinology, 187, 237-247. doi:10.1677/joe.1.06411
[20]	Arafat, H.A., et al. (2007) Osteopontin protects the islets and beta-cells from interleukin-1 beta-mediated cytotoxicity through negative feedback regulation of nitric oxide. Endocrinology, 148, 575-584. doi:10.1210/en.2006-0970
[21]	Lyssenko, V., et al. (2011) Pleiotropic effects of GIP on islet function involve osteopontin. Diabetes, 60, 24242433. doi:10.2337/db10-1532
[22]	Hsieh, M.S., et al. (2010) Dipyridamole suppresses high glucose-induced osteopontin secretion and mRNA expression in rat aortic smooth muscle cells. Circulation Journal, 74, 1242-1250. doi:10.1253/circj.CJ-09-0561
[23]	Wakabayashi, S., et al. (2002) Involvement of phosphodiesterase isozymes in osteoblastic differentiation. Journal of Bone and Mineral Metabolism, 17, 249-256. doi:10.1359/jbmr.2002.17.2.249
[24]	Daiter, E., et al. (1996) Cell differentiation and endogenous cyclic adenosine 3’,5’-monophosphate regulate osteopontin expression in human trophoblasts. Endocrinology, 137, 1785-1790. doi:10.1210/en.137.5.1785
[25]	Cai, Y., et al. (2010) Adrenomedullin up-regulates osteopontin and attenuates vascular calcification via the cAMP/ PKA signaling pathway. Acta Pharmacologica Sinica, 31, 1359-1366. doi:10.1038/aps.2010.89
[26]	Lo, K.W., et al. (2011) The small molecule PKA-specific cyclic AMP analogue as an inducer of osteoblast-like cells differentiation and mineralization. Journal of Tissue Engineering and Regenerative Medicine, 6, 40-48.
[27]	Hohmeier, H.E., et al. (2000) Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion. Diabetes, 49, 424-430. doi:10.2337/diabetes.49.3.424
[28]	Harndahl, L., et al. (2002) Important role of phosphodiesterase 3B for the stimulatory action of cAMP on pancreatic beta-cell exocytosis and release of insulin. The Journal of Biological Chemistry, 277, 37446-37455. doi:10.1074/jbc.M205401200
[29]	Nilsson-Berglund, L.M., et al. (2010) Nuclear factor of activated T cells regulates osteopontin expression in arterial smooth muscle in response to diabetes-induced hyperglycemia. Arteriosclerosis, Thrombosis, and Vascular Biology, 30, 218224. doi:10.1161/ATVBAHA.109.199299
[30]	Brown, K.R. and Jurisica, I. (2007) Unequal evolutionary conservation of human protein interactions in interologous networks. Genome Biology, 8, R95. doi:10.1186/gb-2007-8-5-r95
[31]	Brown, K.R. and Jurisica, I. (2005) Online predicted human interaction database. Bioinformatics, 21, 20762082. doi:10.1093/bioinformatics/bti273
[32]	Wagner, A. and Fell, D.A. (2001) The small world inside large metabolic networks. Proceedings of the Royal Society B: Biological Sciences 268, 1803-1810. doi:10.1098/rspb.2001.1711
[33]	Adamic, L.A. and Huberman, B.A. (2000) Power-law distribution of the world wide web. Science, 287, 2115. doi:10.1126/science.287.5461.2115a
[34]	Smoot, M.E., et al. (2011) Cytoscape 2.8: New features for data integration and network visualization. Bioinformatics, 27, 431-432. doi:10.1093/bioinformatics/btq675
[35]	Bradford, M.M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72, 248-254. doi:10.1016/0003-2697(76)90527-3
[36]	Taira, M. (1993) Molecular cloning of the rat adipocyte hormone-sensitive cyclic GMP-inhibited cyclic nucleotide phosphodiesterase. The Journal of Biological Chemistry, 268, 18573-18579.
[37]	Leibiger, I.B., Leibiger, B. and Berggren, P.O. (2002) Insulin feedback action on pancreatic beta-cell function. FEBS Letters, 532, 1-6. doi:10.1016/S0014-5793(02)03627-X
[38]	Meng, R., Gotz, C. and Montenarh, M. (2010) The role of protein kinase CK2 in the regulation of the insulin production of pancreatic islets. Biochemical and Biophysical Research Communications, 401, 203-206. doi:10.1016/j.bbrc.2010.09.028
[39]	Ashkar, S., et al. (1993) In vitro phosphorylation of mouse osteopontin expressed in E. coli. Biochemical and Biophysical Research Communications, 191, 126-133. doi:10.1006/bbrc.1993.1193
[40]	Francis, S.H., Blount, M.A. and Corbin, J.D. (2011) Mammalian cyclic nucleotide phosphodiesterases: Molecular mechanisms and physiological functions. Physiological Reviews, 91, 651-690. doi:10.1152/physrev.00030.2010
[41]	Rahn Landstrom, T., et al. (2000) Down-regulation of cyclic-nucleotide phosphodiesterase 3B in 3T3-L1 adipocytes induced by tumour necrosis factor alpha and cAMP. Biochemical Journal, 346, 337-343. doi:10.1042/0264-6021:3460337
[42]	Rose, R.J., et al. (1997) Cyclic AMP-mediated regulation of vascular smooth muscle cell cyclic AMP phosphodiesterase activity. British Journal of Pharmacology, 122, 233-240. doi:10.1038/sj.bjp.0701376
[43]	Liu, H. and Maurice, D.H. (1998) Expression of cyclic GMP-inhibited phosphodiesterases 3A and 3B (PDE3A and PDE3B) in rat tissues: Differential subcellular localization and regulated expression by cyclic AMP. British Journal of Pharmacology, 125, 1501-1510. doi:10.1038/sj.bjp.0702227
[44]	Seybold, J., et al. (1998) Induction of phosphodiesterases 3B, 4A4, 4D1, 4D2, and 4D3 in Jurkat T-cells and in human peripheral blood T-lymphocytes by 8-bromocAMP and Gs-coupled receptor agonists. Potential role in beta2-adrenoreceptor desensitization. The Journal of Biological Chemistry, 273, 20575-20588. doi:10.1074/jbc.273.32.20575
[45]	Heimann, E., et al. (2010) Pression and regulation of cyclic nucleotide phosphodiesterases in human and rat pancreatic islets. PLoS One, 5, e14191. doi:10.1371/journal.pone.0014191
[46]	Ahmad, F., et al. (2009) Differential regulation of adipocyte PDE3B in distinct membrane compartments by insulin and the beta3-adrenergic receptor agonist CL316243: Effects of caveolin-1 knockdown on formation/maintenance of macromolecular signalling complexes. Biochemical Journal, 424, 399-410. doi:10.1042/BJ20090842
[47]	Lindh, R., et al. (2007) Multisite phosphorylation of adipocyte and hepatocyte phosphodiesterase 3B. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1773, 584-592. doi:10.1016/j.bbamcr.2007.01.010
[48]	Oknianska, A., et al. (2007) Long-term regulation of cyclic nucleotide phosphodiesterase type 3B and 4 in 3T3-L1 adipocytes. Biochemical and Biophysical Research Communications, 353, 1080-1085. doi:10.1016/j.bbrc.2006.12.141
[49]	Aspinwall, C.A., Lakey, J.R. and Kennedy, R.T. (1999) Insulin-stimulated insulin secretion in single pancreatic beta cells. The Journal of Biological Chemistry, 274, 6360-6365. doi:10.1074/jbc.274.10.6360
[50]	Khoshniat, S., et al. (2011) Phosphate-dependent stimulation of MGP and OPN expression in osteoblasts via the ERK1/2 pathway is modulated by calcium. Bone, 48, 894-902. doi:10.1016/j.bone.2010.12.002