Epidermal Growth Factor Improves the Ultrastructure of Submandibular Salivary Glands of Streptozotocin Induced Diabetic Rats - A Qualitative Study


Mahmoud Al Ankily
Mohamed Shamel
Mahmoud M. Bakr


Diabetes has well known damaging effects on different tissues of the body including salivary glands. Epidermal Growth Factor (EGF) facilitates healing and repair through different mechanisms including the increase in the activation and proliferation of fibroblasts. The aim of this study was to investigate if the effect of EGF was enough to repair the damage caused by diabetes in streptozotocin induced diabetic rats. Sixty adult male albino rats were divided into three groups. A control group, a streptozotocin induced diabetic group, and EGF group that was subjected to a single daily EGF intraperitoneal injection for two months after induction of diabetes. Submandibular salivary glands were dissected and examined using transmission electron microscopy. The diabetic group showed severe signs of atrophy and damage affecting all glandular components. The EGF group showed marked improvement in all elements of the submandibular salivary glands. Conclusions: EGF restored the structural integrity of submandibular salivary glands in diabetic rats.


How to Cite
Al Ankily, M., Shamel, M., & Bakr, M. M. (2020). Epidermal Growth Factor Improves the Ultrastructure of Submandibular Salivary Glands of Streptozotocin Induced Diabetic Rats - A Qualitative Study. International Journal of Medical and Dental Sciences, 9(1), 1803–1810. https://doi.org/10.18311/ijmds/2020/24452


  1. International Diabetes Federation (IDF) Annual Report 2015. Accessed online 29 November 2018. https://www.idf.org/our-activities/advocacy-awareness/resources-andtools/ 58:idf-annual-report-2015.html.
  2. Hasegawa H, Ozawa S, Hashimoto K, et al. Type 2 diabetes impairs implant osseointegration capacity in rats. Int. J. Oral. Maxillofac. Implants. 2008; 23:237-46.
  3. Kwon YB, Kim HW, Roh DH, et al. Topical application of epidermal growth factor accelerates wound healing by myofibroblast proliferation and collagen synthesis in rat. J. Vet. Sei. 2006; 7:105-09. https://doi.org/10.4142/jvs.2006.7.2.105. PMid:16645332, PMCid: PMC3242099.
  4. Cohen S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the newborn animal. J. Biol. Chem. 1962; 237:1555-62.
  5. Oxford GE, Tayari L, Barfoot MD, et al. Salivary EGF levels reduced in diabetic patients. J. Diab. Complications. 2000; 14:140-45. https://doi.org/10.1016/S1056-8727(00)0 0073-8.
  6. Kasayama S, Ohba Y, Oka T. Epidermal growth factor deficiency associated with diabetes mellitus. Proc. Natl. Acad. Sci. USA. 1989; 86:7644-48. https://doi.org/10.1073/ pnas.86.19.7644. PMid: 2477846, PMCid: PMC298123.
  7. Al-Ankily MM, Shamel M, Bakr MM. Epidermal growth factor restores cytokeratin expression in rats with diabetes. J. Res. Med. Dent. Sci. 2018; 6:196-203.
  8. Take G, Ilgaz C, Erdogan D, et al. A comparative study of the ultrastructure of submandibular, parotid and exocrine pancreas in diabetes and fasting. Saudi. Med. J. 2007; 28:2835.
  9. Ohlsson B, Jansen C, Ihse I, et al. Epidermal growth factor induces cell proliferation in mouse pancreas and salivary glands. Department of Surgery. Pancreas. 1997; 14:94-98. https://doi.org/10.1097/00006676-199701000-00014. PMid: 8981513.
  10. Fahim MA, Hasan MY, Alshuaib WB. Cadmium modulates diabetes-induced alterations in murine neuromuscular junction. Endocr. Res. 2000; 26:205-17. https://doi.org/10.3109/07435800009066162. PMid: 10921448.
  11. Mednieks MI, Szczepanski A, Clark B, et al. Protein expression in salivary glands of rats with streptozotocin diabetes. Int. J. Exp. Pathol. 2009;9 0:412-22.
  12. https://doi.org/10.1111/j.1365-2613.2009.00662.x. PMid: 19659899, PMCid: PMC2741151.
  13. Hidayat M, Tahir M, Shoro AA. Melatonin preserves the morphology of parotid gland damaged by streptozotocin induced diabetes. J. Postgrad. Med. Inst. 2004; 28:128-32.
  14. High AS, Sutton J, Hopper AH. A morphometric study of submandibular salivary gland changes in streptozotocininduced diabetic rats. Arch. Oral. Biol. 1985; 30:667-71.
  15. https://doi.org/10.1016/0003-9969(85)90153-0.
  16. Cutler LS, Pinney HE, Christian C, et al. Ultrastructural studies of the rat submandibular gland in streptozotocin induced diabetes mellitus. Virchows Arch. A Pathol. Anat. Histol. 1979; 382:301-11. https://doi.org/10.1007/BF00430406. PMid: 160661.
  17. Lotti LV, Hand AR. Endocytosis of parotid salivary proteins by striated duct cells in streptozotocin diabetic rats. Anat. Rec. 1988; 221:802-11. https://doi.org/10.1002/ ar.1092210404. PMid: 2973265.
  18. Maciejewski R, Burdan F, Hermanowicz-Dryka T, et al. Changes in the activity of some lysosomal enzymes in the fine structure of submandibular gland due to experimental diabetes. Acta. Physiol. Hung. 1999; 86:127-37.
  19. Zeisberg M, Strutz F, Muller GA. Role of fibroblast activation in inducing interstitial fibrosis. J. Nephrol. 2000; 13:S111-20.
  20. Anderson LC, Suleiman AH, Garrett JR. Morphological effects of diabetes on the granular ducts and acini of the rat submandibular gland. Microsc. Res. Tech. 1994; 27:61-70.
  21. https://doi.org/10.1002/jemt.1070270105. PMid: 8155905.
  22. Nagy A, Nagashima H, Cha S, et al. Reduced oral wound healing in the NOD mouse model for type 1 autoimmune diabetes and its reversal by epidermal growth factor supplementation. Diabetes. 2001; 50:2100-04. https://doi.org/10.2337/diabetes.50.9.2100. PMid: 11522677.