title: Ghrelin agonist does not foster insulin resistance but improves cognition in an Alzheimer's disease mouse model.
abstract: 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.
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham AL, USA.|Department of Clinical Research, Max-Planck-Institute of Psychiatry, Munich, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kunath
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham AL, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: van Groen
authors.affiliation: Office of Energetics; Nutrition Obesity Research Center; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham AL, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham AL, USA.
authors.forename: Monique
authors.initials: M
authors.lastname: Dozier-Sharpe
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham AL, USA.
authors.forename: Inga
authors.initials: I
authors.lastname: Kadish
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D054439:Ghrelin / Q000819:agonists*; D018149:Glucose Intolerance / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D065853:Spatial Learning / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin