Ghrelin agonist does not foster insulin resistance but improves cognition in an Alzheimer’s disease mouse model

• Published in: Scientific reports 2015-06, Vol.5 (1), p.11452-11452, Article 11452
• Main Authors: Kunath, Nicolas, van Groen, Thomas, Allison, David B., Kumar, Ashish, Dozier-Sharpe, Monique, Kadish, Inga
• Format: Article
• Language: English
• Subjects: 14/1; 14/63; 59/57; 631/378/1689/132/1283; 692/699/2743/137/138; Alzheimer Disease - metabolism; Alzheimer Disease - psychology; Alzheimer's disease; Animals; Blood Glucose - drug effects; Body fat; Body weight; Body Weight - drug effects; Central nervous system; Cognition; Cognition - drug effects; Dentate Gyrus - drug effects; Dentate Gyrus - metabolism; Dentate Gyrus - pathology; Diabetes mellitus; Disease Models, Animal; Ghrelin; Ghrelin - agonists; Glucose; Glucose Intolerance - metabolism; Glucose tolerance; Hippocampus; Homeostasis; Humanities and Social Sciences; Insulin; Insulin - metabolism; Insulin Resistance; Mice; Microglia - drug effects; Microglia - metabolism; multidisciplinary; Neurodegenerative diseases; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Rodents; Science; Signal Transduction - drug effects; Spatial discrimination learning; Spatial Learning - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep11452

The orexigenic hormone ghrelin, a potential antagonist of the insulin system, ensures sufficient serum glucose in times of fasting. In the race for new therapeutics for diabetes, one focus of study has been antagonizing the ghrelin system in order to improve glucose tolerance. We provide evidence for a differential role of a ghrelin agonist on glucose homeostasis in an Alzheimer’s disease mouse model fed a high–glycemic index diet as a constant challenge for glucose homeostasis. The ghrelin agonist impaired glucose tolerance immediately after administration but not in the long term. At the same time, the ghrelin agonist improved spatial learning in the mice, raised their activity levels and reduced their body weight and fat mass. Immunoassay results showed a beneficial impact of long-term treatment on insulin signaling pathways in hippocampal tissue. The present results suggest that ghrelin might improve cognition in Alzheimer’s disease via a central nervous system mechanism involving insulin signaling.