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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.
