Browse > Article
http://dx.doi.org/10.4062/biomolther.2016.030

Insulin as a Potent Stimulator of Akt, ERK and Inhibin-βE Signaling in Osteoblast-Like UMR-106 Cells  

Ramalingam, Mahesh (Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, Kyung Hee University)
Kwon, Yong-Dae (Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University)
Kim, Sung-Jin (Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, Kyung Hee University)
Publication Information
Biomolecules & Therapeutics / v.24, no.6, 2016 , pp. 589-594 More about this Journal
Abstract
Insulin is a peptide hormone of the endocrine pancreas and exerts a wide variety of physiological actions in insulin sensitive tissues, such as regulation of glucose homeostasis, cell growth, differentiation, learning and memory. However, the role of insulin in osteoblast cells remains to be fully characterized. In this study, we demonstrated that the insulin (100 nM) has the ability to stimulate the phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK) and the levels of inhibin-${\beta}E$ in the osteoblast-like UMR-106 cells. This insulin-stimulated activities were abolished by the PI3K and MEK1 inhibitors LY294002 and PD98059, respectively. This is the first report proving that insulin is a potential candidate that enables the actions of inhibin-${\beta}E$ subunit of the TGF-${\beta}$ family. The current investigation provides a foundation for the realization of insulin as a potential stimulator in survival signaling pathways in osteoblast-like UMR-106 cells.
Keywords
Akt; ERK; Inhibin-${\beta}E$; Insulin; UMR-106;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Aksamitiene, E., Kiyatkin, A. and Kholodenko, B. N. (2012). Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance. Biochem. Soc. Trans. 40, 139-146.   DOI
2 Bergauer, F., Bruning, A., Shabani, N., Blankenstein, T., Juckstock, J., Dian, D. and Mylonas, I. (2009) Inhibin/activin-betaE subunit in normal and malignant human cervical tissue and cervical cancer cell lines. J. Mol. Histol. 40, 353-359.   DOI
3 Cheatham, B. and Kahn, C. R. (1995) Insulin action and the insulin signaling network. Endocr. Rev. 16, 117-142.
4 Crossthwaite, A. J., Hasan, S. and Williams, R. J. (2002) Hydrogen peroxide-mediated phosphorylation of ERK1/2, Akt/PKB and JNK in cortical neurones: dependence on $Ca^{2+}$ and PI3-kinase. J. Neurochem. 80, 24-35.   DOI
5 Ju Ha, H. and Kim, S. J. (2013) Association of insulin receptor and syndecan-1 by insulin with activation of ERK I/II in osteoblast-like UMR-106 cells. J. Recept. Signal Transduct. Res. 33, 37-40.   DOI
6 Kim, J. Y., Lee, J. S., Han, Y. S., Lee, J. H., Bae, I., Yoon, Y. M., Kwon, S. M. and Lee, S. H. (2015) Pretreatment with lycopene attenuates oxidative stress-induced apoptosis in human mesenchymal stem cell. Biomol. Ther. (Seoul) 23, 517-524.   DOI
7 Kim, S. J., Chun, J. Y. and Kim, M. S. (2000) Insulin stimulates production of nitric oxide via ERK in osteoblast cells. Biochem. Biophys. Res. Commun. 278, 712-718.   DOI
8 Kim, S. J. and Kahn, C. R. (1997) Insulin regulation of mitogen-activated protein kinase kinase (MEK), mitogen-activated protein kinase and casein kinase in the cell nucleus: a possible role in the regulation of gene expression. Biochem. J. 323, 621-627.   DOI
9 Kim, S. J. and Kim, K. H. (1997) Insulin rapidly stimulates ERK2 in the membrane of osteoblast-like UMR-106 cell. Biochem. Mol. Biol. Int. 43, 1023-1031.
10 Lee, C. W., Chung, S. W., Bae, M. J., Song, S., Kim, S. P. and Kim, K. (2015) Peptidoglycan up-regulates CXCL8 expression via multiple pathways in monocytes/macrophages. Biomol. Ther. (Seoul) 23, 564-570.   DOI
11 Ramalingam, M. and Kim, S. J. (2016a) The Neuroprotective role of insulin against $MPP^+$-induced parkinson's disease in differentiated SH-SY5Y cells. J. Cell. Biochem. 117, 917-926.   DOI
12 Persad, S., Attwell, S., Gray, V., Mawji, N., Deng, J. T., Leung, D., Yan, J., Sanghera, J., Walsh, M. P. and Dedhar, S. (2001) Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343. J. Biol. Chem. 276, 27462-27469.   DOI
13 Ramalingam, M. and Kim, S. J. (2014) Mechanisms of action of brain insulin against neurodegenerative diseases. J. Neural Transm. (Vienna) 121, 611-626.   DOI
14 Ramalingam, M. and Kim, S. J. (2015) Insulin exerts neuroprotective effects via Akt/Bcl-2 signaling pathways in differentiated SH-SY5Y cells. J. Recept. Signal Transduct. Res. 35, 1-7.   DOI
15 Ramalingam, M. and Kim, S. J. (2016b) Insulin involved Akt/ERK and Bcl-2/Bax pathways against oxidative damages in C6 glial cells. J. Recept. Signal Transduct. Res. 36, 14-20.   DOI
16 Seol, K. C. and Kim, S. J. (2003) Nuclear matrix association of insulin receptor and IRS-1 by insulin in osteoblast-like UMR-106 cells. Biochem. Biophys. Res. Commun. 306, 898-904.   DOI
17 Steiner, D. F. and Oyer, P. E. (1967) The biosynthesis of insulin and a probable precursor of insulin by a human islet cell adenoma. Proc. Natl. Acad. Sci. U.S.A. 57, 473-480.   DOI
18 Wang, L., Yang, H. J., Xia, Y. Y. and Feng, Z. W. (2010) Insulin-like growth factor 1 protects human neuroblastoma cells SH-EP1 against $MPP^+$-induced apoptosis by AKT/GSK-3beta/JNK signaling. Apoptosis 15, 1470-1479.   DOI
19 Duncan, R. and Misler, S. (1989) Voltage-activated and stretch-activated $Ba^{2+}$ conducting channels in an osteoblast-like cell line (UMR 106). FEBS Lett. 251, 17-21.   DOI
20 Delcommenne, M., Tan, C., Gray, V., Rue, L., Woodgett, J. and Dedhar, S. (1998) Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc. Natl. Acad. Sci. U.S.A. 95, 11211-11216.   DOI
21 Han, S. H., Odathurai Saminathan, S. and Kim, S. J. (2010) Insulin stimulates gene expression of ferritin light chain in osteoblast cells. J. Cell. Biochem. 111, 1493-1500.   DOI
22 Zavadil, J., Bitzer, M., Liang, D., Yang, Y. C., Massimi, A., Kneitz, S., Piek, E. and Bottinger, E. P. (2001) Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc. Natl. Acad. Sci. U.S.A. 98, 6686-6691.   DOI
23 Wilkes, M. C., Mitchell, H., Penheiter, S. G., Dore, J. J., Suzuki, K., Edens, M., Sharma, D. K., Pagano, R. E. and Leof, E. B. (2005) Transforming growth factor-beta activation of phosphatidylinositol 3-kinase is independent of Smad2 and Smad3 and regulates fibroblast responses via p21-activated kinase-2. Cancer Res. 65, 10431-10440.   DOI
24 Yan, Z., Winawer, S. and Friedman, E. (1994) Two different signal transduction pathways can be activated by transforming growth factor ${\beta}1$ in epithelial cells. J. Biol. Chem. 269, 13231-13237.
25 Yoon, S. H., Ramalingam, M. and Kim, S. J. (2015) Insulin stimulates integrin-linked kinase in UMR-106 cells: potential role of heparan sulfate on syndecan-1. J. Recept. Signal Transduct. Res. 35, 613-617.   DOI
26 Zhang, Y. E. (2009) Non-Smad pathways in TGF-beta signaling. Cell Res. 19, 128-139.   DOI