This Article Full Text Full Text (PDF) All Versions of this Article: 147/6/2634    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dong, J. Articles by Depoortere, I. Search for Related Content PubMed PubMed Citation Articles by Dong, J. Articles by Depoortere, I.

Role of Endogenous Ghrelin in the Hyperphagia of Mice with Streptozotocin-Induced Diabetes

Center for Gastroenterological Research, Catholic University of Leuven (J.D., T.L.P., B.D.S., P.V.B., I.D.), 3000 Leuven, Belgium; Medical College of Qingdao University (J.D.), Qingdao, China; Johnson & Johnson Pharmaceutical Research and Development, Division of Janssen Pharmaceutica (D.M., B.C.), 2340 Beerse, Belgium; and Laboratory of Biological Chemistry and Nutrition, Université Libre de Bruxelles (C.D.), 1070 Brussels, Belgium

Address all correspondence and requests for reprints to: Dr. Inge Depoortere, Center for Gastroenterological Research, Gasthuisberg O&N, Bus 701, 3000 Leuven, Belgium. E-mail: inge.depoortere{at}med.kuleuven.be.

Ghrelin is an orexigenic peptide involved in the regulation of energy homeostasis. To investigate the role of ghrelin in the hyperphagia associated with uncontrolled streptozotocin-induced diabetes, food intake was followed in diabetic ghrelin knockout (ghrelin^–/–) and control wild-type (ghrelin^+/+) mice and diabetic Naval Medical Research Institute noninbred Swiss mice treated with either saline or the ghrelin receptor antagonist, D-Lys³-GH-releasing peptide-6 (D-Lys³-GHRP-6) for 5 d. In diabetic ghrelin^–/– mice, hyperphagia was attenuated, and the maximal increase in food intake was 50% lower in mutant than in wild-type mice. The increased food intake observed during the light period (1000–1200 h) in ghrelin^+/+ mice was abolished in mutant mice. Diabetic ghrelin^–/– mice lost 12.4% more body weight than ghrelin^+/+ mice. In diabetic ghrelin^+/+ mice, but not in ghrelin^–/– mice, the number of neuropeptide Y (NPY)-immunoreactive neurons was significantly increased. Diabetic Naval Medical Research Institute noninbred Swiss mice were hyperphagic and had increased plasma ghrelin levels. Treatment with D-Lys³-GHRP-6 reduced daily food intake by 23% and reversed the increased food intake observed during the light period. The change in the number of NPY- (2.4-fold increase) and -MSH (1.7-fold decrease)-immunoreactive hypothalamic neurons induced by diabetes was normalized by D-Lys³-GHRP-6 treatment. Our results suggest that enhanced NPY and reduced -MSH expression are secondary to the release of ghrelin, which should be considered the underlying trigger of hyperphagia associated with uncontrolled diabetes.

This article has been cited by other articles:

				H. Takahashi, Y. Kurose, M. Sakaida, Y. Suzuki, S. Kobayashi, T. Sugino, M. Kojima, K. Kangawa, Y. Hasegawa, and Y. Terashima Ghrelin differentially modulates glucose-induced insulin secretion according to feeding status in sheep J. Endocrinol., September 1, 2007; 194(3): 621 - 625. [Abstract] [Full Text] [PDF]

				R. W. Gelling Diabetic Hyperphagia--Ghrelin in the Driver's Seat. Endocrinology, June 1, 2006; 147(6): 2631 - 2633. [Full Text] [PDF]