Unacylated as well as acylated ghrelin promotes cell survival and inhibit apoptosis in HIT-T15 pancreatic beta-cells.
Ghrelin is mainly produced by the stomach, although it is expressed in other tissues, including the pancreas. Among its pleiotropic actions, ghrelin prevents the development of diabetes in rats and exerts mitogenic and antiapoptotic effects in different cell types. In addition, a ghrelin-producing epsilon-cell population has been demonstrated in rodent islets, suggesting a direct role in the control of islet cell survival. In this study, we investigated the effect of acylated ghrelin (AG) and unacylated ghrelin (UAG) on cell survival of HIT-T15 pancreatic beta cells. We show that both AG and UAG equally prevented beta cell death induced by serum withdrawal. In addition, both peptides inhibited serum starvation-induced apoptosis. These findings indicate that UAG and AG prevent cell death and apoptosis of pancreatic beta cells. Since only AG, but not UAG, binds the GRLN receptor, a different and as yet unknown receptor is likely involved in these survival mechanisms.
Granata
R
R
Laboratory of Molecular and Cellular Endocrinology, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy. riccarda.granata@unito.it
Settanni
F
F
Trovato
L
L
Destefanis
S
S
Gallo
D
D
Martinetti
M
M
Ghigo
E
E
Muccioli
G
G
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D036361:Peptide Hormones / Q000378:metabolism / Q000494:pharmacology*
D054439:Ghrelin; D036361:Peptide Hormones; C422650:ghrelin, des-n-octanoyl; D000123:Acetyltransferases