Role of growth hormone and insulin-like growth factor-1 in the protective effect of ghrelin in ischemia/reperfusion-induced acute pancreatitis.
Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has been shown to exhibit gastroprotective properties. The aim of present study was to determine whether ghrelin administration protects the pancreas against ischemia/reperfusion-induced pancreatitis and, if so, what is the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this effect. In sham-operated or hypophysectomized rats, acute pancreatitis was induced by pancreatic ischemia followed by reperfusion. Ghrelin (4, 8 or 16 nmol/kg/dose) or IGF-1 (20 nmol/kg/dose) were administered intraperitoneally twice before and during induction of acute pancreatitis. In pituitary-intact rats, treatment with ghrelin attenuated the development of ischemia/reperfusion-induced pancreatitis and this effect was associated with partial reversion of the pancreatitis-evoked decrease in serum concentration of GH and IGF-1. Hypophysectomy eliminated GH from the serum, reduced serum IGF-1 concentration by 90% and increased in the severity of ischemia/reperfusion-induced pancreatitis. Administration of ghrelin was without any beneficial effect in this group of rats. In contrast, administration of IGF-1 in hypophysectomized rats reduced the severity of ischemia/reperfusion-induced pancreatitis in hypophysectomized rats. We conclude that administration of ghrelin inhibits the development of ischemia/reperfusion-induced pancreatitis and this effect is mediated by its influence on the release of GH and IGF-1.
Dembiński
Artur
A
Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Kraków, Poland. mpdembin@cyf-kr.edu.pl
Warzecha
Zygmunt
Z
Ceranowicz
Piotr
P
Cieszkowski
Jakub
J
Pawlik
Wiesław W
WW
Tomaszewska
Romana
R
Kuśnierz-Cabala
Beata
B
Naskalski
Jerzy W
JW
Kuwahara
Atsukazu
A
Kato
Ikuo
I
D000818:Animals; D054439:Ghrelin; D013006:Growth Hormone / Q000097:blood*; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects / Q000293:injuries; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D036361:Peptide Hormones / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000150:complications
D054439:Ghrelin; D036361:Peptide Hormones; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone