ORIGINAL ARTICLE Exogenous Ghrelin Enhances Endocrine and Exocrine Regeneration in Pancreatectomized Rats Mustafa Kerem & Bulent Salman & Sule Ozsoy & Hatice Pasaoglu & Abdulkadir Bedirli & Rifki Haziroglu & Tonguc Utku Yilmaz Received: 19 October 2008 / Accepted: 24 November 2008 / Published online: 11 December 2008 # 2008 The Society for Surgery of the Alimentary Tract Abstract Aim Ghrelin, the most important modulator of endocrine and exocrine pancreatic functions, has a role in the development of islets of Langerhans during embryogenesis. The aim of this study was to evaluate the effects of ghrelin on pancreatic regeneration in rats with 90% pancreatectomy. Materials and Methods Two- to 3-week-old Wistar rats were used in the study. After anesthesia, 90% pancreatectomy was performed. In the ghrelin group, 90% pancreatectomy was performed. Ten nanomoles per kilogram per day of ghrelin was administered intraperitoneally from the first postoperative day. In the antagonist group, 90% pancreatectomy was performed. From the first postoperative day, rats received the ghrelin receptor antagonists and substance P intraperitoneally at 1 μmol/kg. In the control group, 90% pancreatectomy was performed, and intraperitoneal saline was administered. The sham group did not receive pancreatectomy. Eight rats from each group were randomly selected and sacrificed on the second, third, and 30th days. Results Blood glucose levels in pacreatectomized rats were significantly higher than in rats in the sham group. The number of beta islet cells, serum insulin levels, and PDX-1 and cytokeratin staining scores decreased in rats with pancreatectomy when compared to the sham-group rats. In the ghrelin-receiving rats, blood glucose levels tended to decrease from the 15th postoperative day. Ghrelin treatment increased insulin levels, insulin-positive islet cell number, and 5-bromo-2-deoxyuridine and PDX-1 staining, whereas ghrelin antagonist administration resulted in significant decreases in these parameters. Ghrelin treatment significantly improved glucose tolerance test results. Conclusion Exogenous ghrelin administration decreased blood glucose levels after 90% pancreatectomy by increas- ing islet cell numbers and enhancing endocrine and exocrine regeneration. Keywords Pancreatectomy . Ghrelin . Regeneration . Pancreas . Type 3 diabetes Introduction Cells in the islets of Langerhans undergo continuous turnover under physiological conditions. The pancreas is highly responsive to decreases or increases in the total number of β cells and the regulation of functional islet cell mass. 1,2 β cell hyperplasia and hypertrophy occur to compensate for increased insulin demand during pregnancy and obesity or after pancreatectomy and pancreatic inju- J Gastrointest Surg (2009) 13:775–783 DOI 10.1007/s11605-008-0778-2 Kerem M and Salman B contributed equally to this work; Kerem M, Salman B, and Bedirli A designed experiments; Kerem M, Salman B, Pasaoglu H, Ozsoy S, Haziroglu R, and Yilmaz Tu performed experiments; Kerem M, Salman B, and Bedirli A analyzed data; Kerem M, Salman B, and Bedirli A wrote the paper. M. Kerem (*) : B. Salman : A. Bedirli : T. U. Yilmaz Department of General Surgery, Faculty of Medicine, Gazi University, 06510 Besevler, Ankara, Turkey e-mail: mkerem@gazi.edu.tr S. Ozsoy : R. Haziroglu Department of Pathology, Veterinary Faculty, Ankara University, Ankara, Turkey H. Pasaoglu Department of Clinic Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey