| First Author | Jiang Y | Year | 2014 |
| Journal | Mol Vis | Volume | 20 |
| Pages | 872-80 | PubMed ID | 24966659 |
| Mgi Jnum | J:212540 | Mgi Id | MGI:5581749 |
| Citation | Jiang Y, et al. (2014) beta1-adrenergic receptor stimulation by agonist Compound 49b restores insulin receptor signal transduction in vivo. Mol Vis 20:872-80 |
| abstractText | PURPOSE: Determine whether Compound 49b treatment ameliorates retinal changes due to the lack of beta2-adrenergic receptor signaling. METHODS: Using retinas from 3-month-old beta2-adrenergic receptor-deficient mice, we treated mice with our novel beta1-/beta2-adrenergic receptor agonist, Compound 49b, to assess the effects of adrenergic agonists acting only on beta1-adrenergic receptors due to the absence of beta2-adrenergic receptors. Western blotting or enzyme-linked immunosorbent assay (ELISA) analyses were performed for beta1- and beta2-adrenergic receptors, as well as key insulin resistance proteins, including TNF-alpha, SOCS3, IRS-1(Ser307), and IR(Tyr960). Analyses were also performed on key anti- and proapoptotic proteins: Akt, Bcl-xL, Bax, and caspase 3. Electroretinogram analyses were conducted to assess functional changes, while histological assessment was conducted for changes in retinal thickness. RESULTS: A 2-month treatment of beta2-adrenergic receptor-deficient mice with daily eye drops of 1 mM Compound 49b, a novel beta1- and beta2-adrenergic receptor agonist, reversed the changes in insulin resistance markers (TNF-alpha and SOCS3) observed in untreated beta2-adrenergic receptor-deficient mice, and concomitantly increased morphological integrity (retinal thickness) and functional responses (electroretinogram amplitude). These results suggest that stimulating beta1-adrenergic receptors on retinal endothelial cells or Muller cells can compensate for the loss of beta2-adrenergic receptor signaling on Muller cells, restore insulin signal transduction, reduce retinal apoptosis, and enhance retinal function. CONCLUSIONS: Since our previous studies with beta1-adrenergic receptor knockout mice confirmed that the reverse also occurs (beta2-adrenergic receptor stimulation can compensate for the loss of beta1-adrenergic receptor activity), it appears that increased activity in either of these pathways alone is sufficient to block insulin resistance-based retinal cell apoptosis. |
