Early intervention with glucagon-like peptide 1 analog liraglutide prevents @entity3072 in @entity6 db/db XXXX .

@entity2175 @entity3115 @entity6913 @entity6 @entity19 @entity20647 @entity3072 @entity32267 @entity195 @entity4357 @entity3238
UNASSIGNED: Increasing evidence has shown that @entity2175 ( @entity2175 ) is a risk factor for @entity195 . @entity3072 , which consist of hyperphosphorylated tau and misfolded microtubules, is one of the neuropathological hallmarks of @entity195 . Db/db @entity19 , a rodent model of @entity2175 , also exhibited age-dependent @entity3072 . @entity20647 ( @entity20647 ) mimetics, a type of drug used in @entity2175 , has been found to have neuroprotective effects. The aim of this study was to explore the potential effects of liraglutide (a @entity20647 analog), or insulin, on tau phosphorylation in @entity2175 animals. Male db/db @entity19 (3-3.5  weeks) were daily injected subcutaneously with liraglutide (n  =  27), insulin (n  =  27), or saline (n  =  26), and five to seven @entity19 were killed every 2  weeks for analysis of plasma and cerebrospinal (CSF) insulin levels by ELISA, and protein levels in the hippocampal formation by western blot. We found that db/db @entity19 treated with saline exhibited an age-dependent decrease in CSF insulin and an increase in hippocampal tau phosphorylation. @entity32267 injection reversed the CSF insulin to ~1  mIU/L by the end of 8  weeks treatment, and prevented the hyperphosphorylation of tau protein in the hippocampal formation. By contrast, insulin injection had no effects on CSF insulin or phosphorylation of tau protein. In summary, this study indicates that early @entity20647 analog intervention prevented the age-dependent @entity3072 in @entity2175 @entity19 brain, probably by facilitating sequential activation in an insulin signaling pathway reflected in increased basal activation of Akt and basal suppression of @entity6913 . We found that liraglutide, a @entity20647 ( @entity20647 ) analog, prevented the age-dependent @entity3072 in @entity6 db/db @entity19 . We proposed that liraglutide crosses the blood-brain barrier, and binds @entity20647 receptors from which G beta gamma dissociates intracellularly to activate @entity3115 , resulting in activation of Akt, which suppress @entity6913 ( @entity6913 ), and thereby prevents it from phosphorylating tau. IRS-1: insulin receptor substrate 1; @entity3238 : @entity3238 ; @entity3115 : @entity4357 3-kinase.
