This signaling complexity constitutes the substrate of the functional bias observed between agonists
Exendin-4 significantly increased insulin level and phosphorylation of insulin receptor substrate 1 (IRS-1) in rat hippocampus, and could not change the status of tau phosphorylation without insulin in HT22 neurons, suggesting that insulin is required in reduction of tau hyperphosphorylation by GLP-1R agonists (154)
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Revankar, C.M., Cimino, D.F., Sklar, L.A., Arterburn, J.B
Participants and investigators were thus blinded with respect to treatment (liraglutide or placebo) but not dose volume