The Effects of Epidermal Growth Factor on Pancreas in Alloxan- Diabetic Rats: An Ultrastructural Study
DOI:
https://doi.org/10.12970/2310-9971.2013.01.02.1Keywords:
Alloxan, diabetes, EGF, pancreas, ultrastructure.Abstract
To examine the ultrastructural changes of rat pancreas in alloxan induced diabetes mellitus and the follow-up Epidermal Growth Factor treatment. In this study, we used 30 wistar rats. They were divided into three groups; group I: controls, groupII: alloxan induced diabetes mellitus (single intraperitoneal dose 200mg/kg alloxan), group III: diabetes mellitus + EGFtreatment (0.2 ml EGF injected per day for seven days). At the end of the experimental period, animals were sacrificed and their pancreases were removed. The tissue samples were investigated by using electron microscopy techniques. We observed degenerative changes in the β cells, and acinar cells in group II. In contrast, the β cells and acinar cells have revealed positive alterations in the group III. We found that EGF administration on diabetic rats could reserve some of the degenerative changes caused by diabetes.References
[1] Risbud MV, Bhonde RR. Models of pancreatic regeneration in diabetes. Diabetes Res Clin Pract 2002; 58: 155-65. http://dx.doi.org/10.1016/S0168-8227(02)00103-1
[2] Deckert T, Poulsen JE, Larsen M. Prognosis of diabetics with diabetes onset before the age of thirty-one. II. Factors influencing the prognosis. Diabetologia 1978; 14: 371-7. http://dx.doi.org/10.1007/BF01228131
[3] Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984; 310: 356-60. http://dx.doi.org/10.1056/NEJM198402093100605
[4] Hellerstrom C. The life story of the pancreatic B cell. Diabetologia 1984; 26: 393-400. http://dx.doi.org/10.1007/BF00262208
[5] Tourrel C, Bailbe D, Lacorne M, Meile MJ, Kergoat M, Portha B. Persistent improvement of type 2 diabetes in the GotoKakizaki rat model by expansion of the beta-cell mass during theprediabetic period with glucagon-like peptide-1 or exendin-4. Diabetes 2002; 51: 1443-52. http://dx.doi.org/10.2337/diabetes.51.5.1443
[6] Meier JJ, Bhushan A, Butler AE, Rizza RA, Butler PC. Sustained beta cell apoptosis in patients with long-standing type1 diabetes: indirect evidence for islet regeneration? Diabetologia 2005; 48: 2221-8. http://dx.doi.org/10.1007/s00125-005-1949-2
[7] Meier JJ, Butle AE, Galasso R, Rizza RA, Butler PC. Increased islet beta cell replication adjacent to intrapancreaticgastrinomas in humans. Diabetologia 2006; 49: 2689-96. http://dx.doi.org/10.1007/s00125-006-0410-5
[8] Meier JJ, Lin JC, Butler AE, Galasso R, Martinez DS, Butler PC. Direct evidence of attempted beta cell regeneration in an 89-year-old patient with recent-onset type 1 diabetes. Diabetologia 2006; 49: 1838-44. http://dx.doi.org/10.1007/s00125-006-0308-2
[9] Trucco M, Giannoukakis N. Type 1 diabetes: MHC tailored for diabetes cell therapy. Gene Ther 2005; 12: 553-4. http://dx.doi.org/10.1038/sj.gt.3302431
[10] Jensen J. Gene regulatory factors in pancreatic development. Dev Dyn 2004; 229: 176-200. http://dx.doi.org/10.1002/dvdy.10460
[11] Wells JM. Genes expressed in the developing endocrine pancreas and their importance for stem cell and diabetes research. Diabetes Metab Res Rev 2003; 19: 191-201. http://dx.doi.org/10.1002/dmrr.364
[12] Denhardt DT. Signal-transducing protein phosphorylationcascades mediated by Ras/Rho proteins in the mammalian cell: thepotential for multiplex signalling. Biochem J 1996; 318: 729-47.
[13] Widmann C, Gibson S, Jarpe MB, Johnson GL. Mitogenactivated protein kinase: conservation of a three-kinasemodule from yeast to human. Physiol Rev 1999; 79: 143-80.
[14] Cohen S. The epidermal growth factor (EGF). Cancer 1983; 51: 1787-91. http://dx.doi.org/10.1002/1097- 0142(19830515)51:103.0.CO;2-A
[15] Cohen S, Carpenter G, King L Jr. Epidermal growth factorreceptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity. J Biol Chem 1980; 255: 4834-42.
[16] Cohen S, Carpenter G, King LJR. Epidermal growth factorreceptor-protein kinase interactions. Prog Clin Biol Res 1981; 66: 557-67.
[17] Porte D Jr, Kahn SE. Beta-cell dysfunction and failure in type 2 diabetes: potential mechanisms. Diabetes 2001; 50(Suppl 1): 160-3. http://dx.doi.org/10.2337/diabetes.50.2007.S160
[18] Rosenberg L. Induction of islet cell neogenesis in the adult pancreas: the partial duct obstruction model. Microsci Res Tech 1988; 43: 337-46. http://dx.doi.org/10.1002/(SICI)1097- 0029(19981115)43:43.0.CO;2-U
[19] Vinik A, Rafaeloff R, Pittenger G, Rosenberg L, Dugwid W. Induction of pancreatic islet neogenesis. Horm Metab Res 1997; 29: 278-93. http://dx.doi.org/10.1055/s-2007-979037
[20] Sarvetnick NE, Gu D. Regeneration of pancreatic endocrine cells in interferon-gamma transgenic mice. Adv Exp Med Biol 1992; 321: 85-9. http://dx.doi.org/10.1007/978-1-4615-3448-8_10
[21] Papaccio G, Linn T, Federlin K, Volkman A, Esposito V, Mezzogiorno V. Further morphological and biochemical observations on early low dose streptozotocin diabetes in mice. Pancreas 1991; 6; 659-67. http://dx.doi.org/10.1097/00006676-199111000-00007
[22] Path G, Opel A, Gehlen M, et al. Glucose-dependent expansion of pancreatic beta-cells byhe protein p8 in vitro and in vivo. Am J Physiol Endocrinol Metab 2006; 291: 1168- 76. http://dx.doi.org/10.1152/ajpendo.00436.2005
[23] Garcia-Ocana A, Takane KK, Syed MA, Philbrick WM, Vasavada RC, Stewart AF. Hepatocyte growth factor overexpression in the islet of transgenic mice increases beta cell proliferation, enhances islet mass, and induces mild hypoglycemia. J Biol Chem 2000; 275: 1226-32. http://dx.doi.org/10.1074/jbc.275.2.1226
[24] Kayali AG, Stotland A, Gunst KV, Kritzik M, Liu G, Dabernat S. Growth factor-induced signaling of the pancreatic epithelium. J Endocrinol 2005; 185: 45-56. http://dx.doi.org/10.1677/joe.1.05949
[25] Höög A, Hu W, Abdel-Halim SM, Falkmer S, Qing L Grimelius L. Ultrastructural localization of insulin-like growth factor-2 (IGF-2) to thesecretory granules of insulin cells: a study in normal and diabetic (GK) rats. Ultrastruct Pathol 1997; 21: 457-66.
[26] Corrons FJ, Camihort GA, Gómez Dumm CL, Epstein PN, Gagliardino JJ. Structure and ultrastructure of the endocrine pancreas in diabetic transgenic mice. Medicina 1996; 56: 666-70.
[27] Miyahara T, Kawabuchi M, Goto M, Nakano I, Nada O, Nawata H. Morphological study of pancreatic endocrine in an experimental chronicpancreatitis with diabetes induced by stress and cerulein. Ultrastruct Pathol 1999; 23: 171-80. http://dx.doi.org/10.1080/019131299281671
[28] Hong EG, Noh HY, Lee SK, Chung YS, Lee KW, Kim HN. Insulin and glukagon secretions, and morphological change ofpancreatic islets in OLETF rats, a model of type 2 diabetes mellitus. J Korean Med Sci 2002; 17: 34-40.
[29] Aughsten AA. An ultrastructural study on the effect of streptozotocin on the islets of Langerhans in mice. J Electron Microsc 2000; 49: 681-90. http://dx.doi.org/10.1093/oxfordjournals.jmicro.a023859
[30] Bolkent S, Yanardag R, Tabakoglu OA, Ozsoy SO. Effects of chard (Beta vulgaris L.var. cicla) extract on pancreatic B cells in streptozotocin-diabetic rats: a morphological and biochemical study. J Ethnopharmacol 2000; 73: 251-9. http://dx.doi.org/10.1016/S0378-8741(00)00328-7
[31] Maciejewski R, Kopieniak M, Madej B, Sek A, Dabrowski A. Acid phosphatase activity in different organs as a marker of acute pancreatitis. Ann Univ Mariae Curie Sklodowska 2001; 56: 356-61.
