Role of endogenous ghrelin in the hyperphagia of mice with streptozotocin-induced diabetes.

Abstract

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 alpha-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 alpha-MSH expression are secondary to the release of ghrelin, which should be considered the underlying trigger of hyperphagia associated with uncontrolled diabetes.

• Authors: J Dong, T L Peeters, B De Smet, D Moechars, C Delporte, P Vanden Berghe, B Coulie, M Tang, I Depoortere
• Journal: Endocrinology (Endocrinology) Vol. 147 Issue 6 Pg. 2634-42 (Jun 2006) ISSN: 0013-7227 [Print] United States
• PMID: 16484325 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Ghrelin
• Neuropeptide Y
• Oligopeptides
• Peptide Hormones
• growth hormone releasing hexapeptide
• alpha-MSH
• Streptozocin
• Glucagon

Topics

• Animals
• Arcuate Nucleus of Hypothalamus (physiology)
• Blood Glucose (analysis)
• Body Weight
• Diabetes Mellitus, Experimental (complications)
• Ghrelin
• Glucagon (blood)
• Hyperphagia (etiology)
• Male
• Mice
• Mice, Inbred C57BL
• Neuropeptide Y (analysis, physiology)
• Oligopeptides (pharmacology)
• Peptide Hormones (blood, physiology)
• Streptozocin
• alpha-MSH (analysis)