Abstract
Purpose: :
To determine whether beta-adrenergic receptor stimulation, insulin stimulation or the combined stimulation can regulate IGF-1 receptor signaling in human retinal endothelial cells.
Methods: :
Retinal endothelial cells were grown in high glucose medium and treated with xamoterol alone, insulin alone or with both insulin +xamoterol. The treated and non-treated cell lysates were used to examine the role of xamoterol alone, insulin alone, and with both insulin + xamoterol in the regulation of total and phosphorylated IGF-1 receptor, insulin receptor beta, Akt, and caspase 3. TUNEL analyses were done to verify apoptosis.
Results: :
Xamoterol reduced IGF-1R, Akt and insulin levels. Insulin significantly increased IGF-1R, Akt, insulin receptor and total insulin levels. Combined treatments increased IGF-1R, Akt and insulin receptor levels in acute treatments, but the response was short. Caspase-3 activity is decreased with all treatments.
Conclusions: :
The data suggest that beta-adrenergic receptors and insulin stimulation regulate IGF-1 receptor signaling in retinal endothelial cells. Insulin reduced apoptosis and the cleavage of caspase 3 levels, likely through increased IGF-1 receptor phosphorylation. While xamoterol also reduced apoptosis, this response did not occur through IGF-1 receptor signaling. When insulin and xamoterol treatments are combined, IGF-1 receptor signaling is likely regulated primarily through insulin actions.
Keywords: growth factors/growth factor receptors • neurotransmitters/neurotransmitter systems • diabetic retinopathy