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the last has shown biased agonism with reduced -arrestin-mediated receptor internalisation in preclinical studies [84,85,86]

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Binding of free insulin to the cell membrane-bound IR results in activation of the intrinsic tyrosine kinase of insulin receptor (IR) then phosphorylates the -subunit of IR which stimulates activation of the insulin signaling cascade through PI3K and AKT, ultimately leading to translocation of the glucose transporter 4 to the cell membrane of skeletal muscle and adipose cells and uptake of glucose (Styskal et al., 2012)