title: Role of ghrelin in streptozotocin-induced diabetic hyperphagia.
abstract: Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, was originally purified from the rat stomach. We have previously reported that central administration of ghrelin increases food intake and body weight. To investigate the role of ghrelin in the hyperphagic response to uncontrolled diabetes, adult male rats were studied 14 days after administration of streptozotocin (STZ) or vehicle. STZ-treated diabetic rats were markedly hyperphagic. This hyperphagia was accompanied by hyperglycemia, hypoinsulinemia, and reduced plasma GH levels. Treatment of diabetic rats with insulin reversed these changes. Plasma ghrelin concentrations in untreated diabetic rats were significantly higher than in control rats and were normalized by insulin treatment. The ghrelin gene expression in the stomach was also higher in STZ diabetic rats than in control rats, but this difference was not significant. In contrast, plasma leptin was markedly reduced in STZ diabetic rats. This reduction in plasma leptin levels was reversed by insulin treatment. In addition, hypothalamic NPY mRNA levels were increased in STZ-treated diabetic rats and were reversed by insulin treatment. Furthermore, the hyperphagia was partially reversed by the administration of a ghrelin-receptor antagonist. Therefore, we conclude that the elevated plasma ghrelin levels, along with decreased plasma leptin levels, could contribute to the diabetic hyperphagia in part by increasing hypothalamic NPY. This is the first report to show the pathophysiological significance of ghrelin in diabetes.
authors.affiliation: Department of Medicine, Nippon Medical School, Tokyo 113-8603, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ishii
authors.forename: Jun
authors.initials: J
authors.lastname: Kamegai
authors.forename: Hideki
authors.initials: H
authors.lastname: Tamura
authors.forename: Takako
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sugihara
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oikawa
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D005753:Gastric Mucosa / Q000378:metabolism; D015870:Gene Expression; D054439:Ghrelin; D013006:Growth Hormone / Q000097:blood; D006963:Hyperphagia / Q000188:drug therapy / Q000209:etiology*; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D020738:Leptin / Q000097:blood; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000502:physiology; D036361:Peptide Hormones / Q000097:blood / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y; D036361:Peptide Hormones; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013006:Growth Hormone