Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats.

AIMS/HYPOTHESIS: 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/INTERPRETATION: 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.

Plasma ghrelin levels in healthy elderly volunteers: the levels of acylated ghrelin in elderly females correlate positively with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure.

Aging is associated with a decrease in growth hormone (GH) secretion, appetite and energy intake. As ghrelin stimulates both GH secretion and appetite, reductions in ghrelin levels may be involved in the reductions in GH secretion and appetite observed in the elderly. However, only preliminary studies have been performed on the role of ghrelin in elderly subjects. In this study, we sought to clarify the physiologic implications of the age-related alterations in ghrelin secretion by determining plasma ghrelin levels and other clinical parameters in healthy elderly subjects. Subjects were > or = 65 years old, corresponding to the SENIEUR protocol, had not had a resection of the upper gastrointestinal tract and had not been treated with hormones. One hundred and five volunteers (49 men and 56 women) were admitted to this study (73.4 +/- 6.3 years old). Plasma levels of acylated ghrelin in elderly female subjects positively correlated with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure. In elderly men, desacyl ghrelin levels correlated only weakly with bowel movement frequency. These findings suggest that the plasma levels of the acylated form of ghrelin may influence the age-related alterations in GH/IGF-I regulation, blood pressure and bowel motility. These observational associations warrant further experimental studies to clarify the physiologic significance of these effects.