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 beta-cell death and to improve beta-cell function under treatment with cytokines, which are major cause of beta-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 beta-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 beta-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 beta-cell function.
Granata
Riccarda
R
Division of Endocrinology, Diabetology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy. riccarda.granata@unito.it
Volante
Marco
M
Settanni
Fabio
F
Gauna
Carlotta
C
Ghé
Corrado
C
Annunziata
Marta
M
Deidda
Barbara
B
Gesmundo
Iacopo
I
Abribat
Thierry
T
van der Lely
Aart-Jan
AJ
Muccioli
Giampiero
G
Ghigo
Ezio
E
Papotti
Mauro
M
D000818:Animals; D000831:Animals, Newborn; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D054439:Ghrelin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D036361:Peptide Hormones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D054439:Ghrelin; D036361:Peptide Hormones; D019253:Proto-Oncogene Proteins c-bcl-2; C505798:obestatin, rat