β1-adrenergic receptor stimulation by agonist Compound 49b restores insulin receptor signal transduction in vivo.

摘要: Purpose Determine whether Compound 49b treatment ameliorates retinal changes due to the lack of β2-adrenergic receptor signaling. Methods Using retinas from 3-month-old receptor-deficient mice, we treated mice with our novel β1-/β2-adrenergic agonist, 49b, assess effects adrenergic agonists acting only on β1-adrenergic receptors absence receptors. Western blotting or enzyme-linked immunosorbent assay (ELISA) analyses were performed for β1- and receptors, as well key insulin resistance proteins, including TNF-α, SOCS3, IRS-1(Ser307), IR(Tyr960). Analyses also anti- proapoptotic proteins: Akt, Bcl-xL, Bax, caspase 3. Electroretinogram conducted functional changes, while histological assessment was in thickness. Results A 2-month daily eye drops 1 mM a reversed markers (TNF-α SOCS3) observed untreated concomitantly increased morphological integrity (retinal thickness) responses (electroretinogram amplitude). These results suggest that stimulating endothelial cells Muller can compensate loss signaling cells, restore signal transduction, reduce apoptosis, enhance function. Conclusions Since previous studies knockout confirmed reverse occurs (β2-adrenergic stimulation activity), it appears activity either these pathways alone is sufficient block resistance-based cell apoptosis.