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

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+/+)...

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Published in:Endocrinology (Philadelphia) 2006-06, Vol.147 (6), p.2634-2642
Main Authors: Dong, J, Peeters, T. L, De Smet, B, Moechars, D, Delporte, C, Vanden Berghe, P, Coulie, B, Tang, M, Depoortere, I
Format: Article
Language:English
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Summary: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 α-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 α-MSH expression are secondary to the release of ghrelin, which should be considered the underlying trigger of hyperphagia associated with uncontrolled diabetes.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2005-1335