Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats
The ghrelin gene products, namely acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob), were shown to prevent pancreatic β-cell death and to improve β-cell function under treatment with cytokines, which are major cause of β-cell destruction in diabetes. Moreover, AG had been described previously to prevent streptozotocin (STZ)-induced diabetes in rats; however, the effect of either UAG or Ob has never been examined in this context. In the present study, we investigated the potential of UAG and Ob to increase islet β-cell mass and to reduce diabetes at adult age in STZ-treated neonatal rats. One-day-old rats were injected with STZ and subsequently administered with either AG, UAG or Ob for 7 days. On day 70, plasma glucose levels, plasma and pancreatic insulin levels, pancreatic islet area and number, insulin and pancreatic/duodenal homeobox-1 (Pdx1) gene expression, and antiapoptotic BCL2 protein expression were determined. Similarly to AG, both UAG and Ob counteracted STZ-induced high glucose levels and improved plasma and pancreatic insulin levels, which were reduced by the diabetogenic compound. UAG and Ob increased islet area, islet number, and β-cell mass with respect to STZ treatment alone. Finally, in STZ-treated animals, UAG and Ob up-regulated insulin and Pdx1 mRNA and increased the expression of BCL2 similarly to AG. Taken together, our results suggest that in STZ-treated newborn rats, UAG and Ob improve glucose metabolism and preserve islet cell mass, granting a therapeutic potential in medical conditions associated with impaired β-cell function.
|Keywords||PDX1 gene, animal experiment, animal model, animal tissue, article, cell death, cell destruction, cell protection, controlled study, diabetes mellitus, gene expression, ghrelin, glucose, glucose blood level, glucose homeostasis, homeobox, hormonal regulation, immunohistochemistry, insulin, insulin release, messenger RNA, newborn, nonhuman, obestatin, pancreas islet cell, priority journal, protein bcl 2, rat, real time polymerase chain reaction, streptozocin diabetes|
|Persistent URL||dx.doi.org/10.1677/JME-09-0141, hdl.handle.net/1765/20659|
|Journal||Journal of Molecular Endocrinology|
Granata, R, Volante, M, Settanni, F, Gauna, C, Ghé, C, Annunziata, M, … Papotti, M. (2010). Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats. Journal of Molecular Endocrinology, 45(1), 9–17. doi:10.1677/JME-09-0141