Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats.
OBJECTIVE
Ghrelin, a stomach-derived hormone, functions in multiple biological processes, including glucose metabolism and cellular differentiation and proliferation. In this study, we examined whether early treatment with ghrelin can regenerate beta cells of the pancreas in an animal model of diabetes mellitus, the n0-STZ model, in which neonatal rats are injected with streptozotocin (STZ) at birth.


METHODS
Following administration of ghrelin to n0-STZ rats from postnatal days 2 to 8, we examined beta cell mass, mRNA expression levels of insulin and of pancreatic and duodenal homeobox 1 (Pdx1) gene, and pancreatic morphology on days 21 and 70. In addition, we investigated the effects of ghrelin on beta cell replication.


RESULTS
By day 21, ghrelin treatment increased pancreatic expression of insulin and Pdx1 mRNA in n0-STZ rats. The number of replicating cells was also significantly increased in the ghrelin-treated n0-STZ model. At day 70, n0-STZ rats exhibited hyperglycaemia, despite slight increases in plasma insulin levels. Ghrelin treatment resulted in the improvement of plasma glucose levels, which were associated with normal plasma insulin levels. Pancreatic insulin mRNA and protein levels were significantly increased in ghrelin-treated n0-STZ model animals.


CONCLUSIONS
These findings suggest that ghrelin promotes regeneration of beta cells in STZ-treated newborn rats. Thus, early administration of ghrelin may help prevent the development of diabetes in disease-prone subjects after beta cell destruction.
Irako
T
T
Ghrelin Research Project, Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto University School of Medicine, Kyoto, Japan.
Akamizu
T
T
Hosoda
H
H
Iwakura
H
H
Ariyasu
H
H
Tojo
K
K
Tajima
N
N
Kangawa
K
K
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D005260:Female; D054439:Ghrelin; D007328:Insulin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology; D008297:Male; D036361:Peptide Hormones / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin / Q000494:pharmacology
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D013311:Streptozocin