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Exogenous Ghrelin Enhances Endocrine and Exocrine Regeneration in Pancreatectomized Rats

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Journal of Gastrointestinal Surgery

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 increasing islet cell numbers and enhancing endocrine and exocrine regeneration.

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Acknowledgments

This study was supported by a grant from The Scientific and Technological Research Council of Turkey Ankara, Turkey. Project No: SBAG-HD-154 (106S231). This study was presented at the Turkish National Surgical Congress, May 2008, Antalya, Turkey

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Correspondence to Mustafa Kerem.

Additional information

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.

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Kerem, M., Salman, B., Ozsoy, S. et al. Exogenous Ghrelin Enhances Endocrine and Exocrine Regeneration in Pancreatectomized Rats. J Gastrointest Surg 13, 775–783 (2009). https://doi.org/10.1007/s11605-008-0778-2

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