Title: Induced To Differentiation and Morphogenesis of Pancreatic Islet Clusters: Effects on Glycated Fetal Bovine Serum

Authors: Sivalingam Murugan, Ikuo Nishigaki, Gowri Rangasamy Gunassekaran, Ganapathy Ekambaram, Kalpana Deepa Priya Dorayappan, Vishal Babu, Ameesh Madhusoodhanan Nair

 DOI:  http://dx.doi.org/10.18535/jmscr/v4i5.17

Abstract

Mouse embryonic stem cells (MESCs) are potency to differentiate into mature pancreatic islet cells and using for tissue repair treatment. Advanced glycation end-products (AGEs) are accrual of long lived proteins of various tissues and have been implicated in chronic complications in diabetes mellitus, but the pathogenic role of AGEs on pancreatic islet cells is remains unclear. Stem cell differentiation is carried out based on standard protocol followed in the laboratory.  In results the differentiated stem cells shows extensive self-renewal capacity and grow in highly viable for long term in the culture media, had remarkable size, formed aggregates, which built tissue like structures and closer examination by light microscopy analysis revealed islet cell like morphology. Administration of GFBS +iron on induced pancreatic islet cells is observed induce charity of cells. Conclusion this findings demonstrate that AGEs directly cause insulin secretory defects and toxicity, most likely by impairing pancreatic cell functions, which may contribute to the development of diabetes. This approach offers a promising an ample supply of insulin producing cells for cell transplantation therapy and maintains the complication factors in diabetic mellitus, suggesting that further improvement is needed.

Keywords: Embryonic stem cell, insulin producing cell, diabetes, Glycated bovine albumin

References

    

1.      International Diabetes Federation (IDF). IDF Diabetes Atlas Update Poster, 6th ed.; International Diabetes Federation: Brussels, Belgium, 2014.

2.      Morrish, N. Wang, S.L. Stevens, L. Fuller, J. Keen, H. Mortality and causes of death in the who multinational study of vascular disease in diabetes. Diabetologia, 2001, 44: 14-21.

3.      Johnson, B.V.N. Shindo, P.D. Rathjen, J. Rathjen, J. Keough R.A. Understanding pluripotency- how embryonic stem cells keep their options open. Molecular Human Reproduction, 2008,14(9):513–520.

4.      Qiuju Liu, Liang Sun, Yi Tan, Guanjun Wang, Xu Lin, and Lu Cai. Role of Iron Deficiency and Overload in the Pathogenesis of Diabetes and Diabetic Complications. Current Medicinal Chemistry, 2009, 16: 113-129.

5.      Wei, J. Yan Shi, Dongxin Zhao, Song Chen, Jun Yong, Jing Zhang, Tingting Qing, Xiaoning Sun, Peng Zhang, Mingxiao Ding, Dongsheng Li, Hongkui Deng. In vitro derivation of functional insulin producing cells from human embryonic stem cells. Cell Research, 2007, 17: 333-344.

6.      Nadya Lumelsky, Olivier Blondel, Pascal Laeng, Ivan Velasco, Rea Ravin, Ron McKay. Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets. Science, 2001, 292(18): 1389-1394.

7.      Rondeau, P. Navara, G. Militello, V. Bourdon, E. On the aggregation of albumin: Influences of the protein glycation. In protein aggregation. Edited by Douglas A, Stein Nova Science publishers, in 2010.

8.      Kerstin Nowotny, Tobias Jung, Annika Höhn, Daniela Weber and Tilman Grune. Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus. Biomolecules, 2015, 5: 194-222.

9.      Cellek, S. Point of NO return for intrinsic nerves in diabetes: a new insight into diabetic complications. Curr. Pharm. Des., 2004, 10: 3683-3695.

10.  Denis, U. Lecomte, M. Paget, C. Ruggiero, D. Wiernsperger, N. Lagarde, M. Advanced glycation end-products induce apoptosis of bovine retinal pericytes in culture: involvement of diacylglycerol/ ceramide production and oxidative stress induction. Free Radic. Biol. Med.,2002, 33: 236-247.

11.  Ramasamy, R. Vannucci, S.J. Yan, S.S. Herold, K. Yan, S.F. Schmidt, A.M. Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology, 2005, 15:16- 28.

12.  Wilson, J.G. Lindquist, J.H. Grambow, S.C. Crook, E.D. Maher, J.F. Potential role of increased iron stores in diabetes. Am. J. Med. Sci., 2003, 325: 332-9.

13.  Beutler, E. Hoffbrand, A.V. Cook, J.D. Iron deficiency and overload. Hematology. Am. Soc. Hematol. Educ. Program, 2003, 40-61.

14.  Swaminathan, S. Fonseca, V.A. Alam, M.G. Shah, S.V. The role of iron in diabetes and its complications. Diabetes Care, 2007, 30: 1926-33.

15.  Rajpathak, S.N. Crandall, J.P. Wylie Rosett, J. Kabat, G.C. Rohan, T.E. Hu, F.B. The role of iron in type 2 diabetes in humans. Biochim. Biophys. Acta, 2009, 1790(7):671-681.

16.  Ikuo Nishigaki, Gowri Rangasamy Gunassekaran, Panjan Nagappan Venkatesan, Mandupal haco Sabu, Sabu Priya, Peramaiyan Rajendran, Dhanapal Sakthisekaran and Yutaka Nishigaki. Stimulatory Role of Glycated Fetal Bovine Serum Along with Iron on in vitro Production of Insulin by Differentiated Mouse Embryonic Stem Cells. Journal of Health Science, 2011, 57(4): 356-361.

17.  Zhixin, L. I. Matthew, R. Barron, J. L. and Ming. Rapid single-step separation of pluripotent mouse embryonic stem cells from mouse feeder fibroblasts. Stem Cells Dev., 2008, 17: 383-387.

18.  Yamashita J, Hiroshi Itoh, Masanori Hirashima, Minetaro Ogawa, Satomi Nishikawa, Takami Yurugi, Makoto Naito, Kazuwa Nakao and Shin-Ichi Nishikawa. Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature, 2000, 408: 92-96

19.  Lee, S.H. Lumelsky, N. Studer, L. Auerbach, J.M. McKay, R. D. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol., 2000,18(6):675-9.

20.   Halban, P. A. Powers, S. L. George, K.L. Bonner Weir, S. Spontaneous reassociation of dispersed adult rat pancreatic islet cells into aggregates with three-dimensional architecture typical of native islets. , 1987, 36(7):783-90.

21.  Rajagopal, J. Anderson, W. J. Kume, S. Martinez, O. I. Melton, D. A. Insulin staining of ES cell progeny from insulin uptake. Science, 2003, 299(5605):363.

22.  Zulewski, H. Abraham, E.J. Gerlach, M.J. Daniel, P.B. Moritz, W. Muller, B. Vallejo, M. Thomas, M.K. Habener, J.F. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine and hepatic phenotypes. Diabetes, 2001, 50: 521-533.

23.  Kolb, H. Burkart, V. Nicotinamide in type 1 diabetes: Mechanism of action revisited. Diabetes Care, 1999, 22(2):16-20.

24.  Luciano Viviani, G. Puddu, A. Sacchi, G. Garuti, A. Storace, D. Durante, A. Monacelli, F. Odetti, P. Glycated fetal calf serum affects the viability of an insulin secreting cell line in vitro. Metabolism, 2008, 57: 163-169.

25.  Zhao, Z. Zhao, C. Zhang, X.H. Zheng, F. Cai, W. Vlassara, H. Ma, Z.A. Advanced glycation end products inhibit glucose-stimulated insulin secretion through nitric oxide-dependent inhibition of cytochrome C oxidase and adenosine triphosphate synthesis. Endocrinology, 2009, 150:2569-2576.

26.  Lin, N. Zhang, H. Su, Q. Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress. Diabetes Metab., 2012, 38: 250-257.

27.  Zhu, Y. Shu, T. Lin, Y. Wang, H; Yang, J. Shi, Y. Han, X. Inhibition of the receptor for advanced glycation end products (RAGE) protects pancreatic beta cells. Biochem. Biophys.  Res. Commun., 2011, 404: 159-165.

28.  Rajpathak, S. Ma, J. Manson, J. Willett, W.C. Hu, F.B. Iron intake and the risk of type 2 diabetes in women: a prospective cohort study. Diabetes Care, 2006, 29: 1370-6.

29.  Wrede, C.E. Buettner, R. Bollheimer, L.C. Scholmerich, J. Palitzsch, K.D. Hellerbrand, C. Association between serum ferritin and the insulin resistance syndrome in a representative population. Eur. J. Endocrinol., 2006, 154: 333-40.

30.  Ana Flavia, S. Sampaio, Maisa Silva, Waleska, C. Dornas Daniela, C. Costa, Marcelo, E. Silva, Rinaldo, C. dos Santos, Wanderson, G. de Lima, Maria Lucia Pedrosa. Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes. Biometals, 2014, 27(2):349-361.

Corresponding Author

Ikuo Nishigaki

Director, NPO International Laboratory of Biochemistry, 1–166 Uchide, Nakagawa-ku,

Nagoya 454–0926, Japan

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