Ghrelin prevents the development of experimental diabetic neuropathy in rodents.

Ghrelin is an acylated peptide discovered in gastric extracts as an endogenous ligand for the growth hormone secretagogue (GHS) receptor. This peptide increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. Our study investigated the pharmacological effect of ghrelin in the prevention of polyneuropathy in streptozotocin-induced diabetes mellitus in C57BL/6N mice, GHS receptor-deficient mice, and growth hormone-deficient rats. Ghrelin or desacyl-ghrelin was administered daily for four weeks immediately after disease onset. The effects of ghrelin on food intake, body weight, blood glucose and plasma insulin levels, nerve conduction velocities, temperature sensation, and 8-isoprostaglandin F2α (8-iso-PGF2α) levels were examined. We found that ghrelin administration did not change food intake, body weight gain, blood glucose levels, or plasma insulin levels in C57BL/6N mice in comparison with mice treated with saline or desacyl-ghrelin administration. Ghrelin administration, but not desacyl-ghrelin, prevented motor and sensory polyneuropathy and reduced the plasma concentrations of 8-iso-PGF2α in C57BL/6N mice. Ghrelin also prevented the reduction in nerve conduction velocities in growth hormone-deficient rats, but not in GHS receptor-knockout mice. In conclusion, ghrelin administration in a rodent model of diabetes prevented polyneuropathy, and this effect was mediated through the GHS receptor and was independent of growth hormone. The protection against the development of experimental diabetic polyneuropathy by ghrelin could be key in preventing this otherwise intractable disorder.