Exogenous ghrelin enhances endocrine and exocrine regeneration in pancreatectomized rats.
OBJECTIVE
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.


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 mumol/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.


CONCLUSIONS
Exogenous ghrelin administration decreased blood glucose levels after 90% pancreatectomy by increasing islet cell numbers and enhancing endocrine and exocrine regeneration.
Kerem
Mustafa
M
Department of General Surgery, Faculty of Medicine, Gazi University, 06510 Besevler, Ankara, Turkey. mkerem@gazi.edu.tr
Salman
Bulent
B
Ozsoy
Sule
S
Pasaoglu
Hatice
H
Bedirli
Abdulkadir
A
Haziroglu
Rifki
R
Yilmaz
Tonguc Utku
TU
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002452:Cell Count; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D054439:Ghrelin / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects; D010180:Pancreatectomy; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*
D001786:Blood Glucose; D054439:Ghrelin