Diabetic retinopathy results from altered insulin receptor signaling. Based on previous studies demonstrating an interaction between β-adrenergic receptors and insulin signaling in hyperglycemic conditions, we hypothesized that β-adrenergic receptor stimulation and insulin stimulation would act synergistically to inhibit one of the hallmarks of diabetic retinopathy, namely retinal endothelial cell apoptosis. To test this hypothesis, human retinal endothelial cells were grown in high glucose (25 mM) medium and treated with a β-1-adrenergic receptor agonist (xamoterol, 10 μM) alone, insulin alone (10 nM) or xamoterol + insulin. We then assessed changes in the levels of insulin receptor, insulin-like growth factor (IGF-1) receptor, and Akt phosphorylation, as well as cleaved caspase 3. Xamoterol alone significantly decreased insulin receptor, IGF-1 receptor and Akt phosphorylation, whereas insulin alone increased insulin receptor, IGF-1 receptor, and Akt phosphorylation. Xamoterol significantly decreased apoptosis of retinal endothelial cells. This data suggests that both β-adrenergic receptors and insulin can inhibit retinal endothelial cell apoptosis in hyperglycemic conditions, but inhibition occurs through independent pathways. These findings have implications for treatments of diabetic retinopathy.
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The authors would like to thank Dr. Dianna Johnson for her help in editing the text. This work is supported by a Career Development Award from JDRF 2-2006-114 (JJS), JDRF Translational Award 17-2008-1044 (JJS), the William and Mary Greve Special Scholars Award from Research to Prevent Blindness and a departmental award from the Research to Prevent Blindness (Dr. Barrett Haik, chair), NEI Vision Core Grant: PHS 3P30 EY013080 (PI: Dianna Johnson).
Special issue article in honor of Dr. Dianna Johnson.
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Panjala, S.R., Steinle, J.J. Insulin and β-adrenergic Receptors Inhibit Retinal Endothelial Cell Apoptosis Through Independent Pathways. Neurochem Res 36, 604–612 (2011). https://doi.org/10.1007/s11064-010-0303-3