FNDC5 and diabetes mellitus: The aim of the present study is to assess (a) whether irisin can exert beneficial effects on the neuropathological changes in DM mice, specifically for astrocyte activation, neuroinflammation, and synaptic protein loss; (b) whether the astrocyte is one of the therapeutic targets of irisin; (c) whether irisin is capable of improving memory and cognitive performance and protecting neurons against astrocyte-mediated neuronal damage; and (d) whether irisin can regulate the signaling pathways which trigger the neuroinflammation cascade.