Diabetes Reduces Basal Retinal Insulin Receptor Signaling

• DOI: 10.2337/diabetes.55.04.06.db05-0744
• Publication Date: 2006-05-08T22:24:58Z
• Authors: Chad E.N. Reiter; Xiaohua Wu; Lakshman Sandiras...; Makoto Nakamura; Kirk A. Gilbert; Ravi S.J. Singh; Patrice E. Fort; David A. Antonetti; Thomas W. Gardner
• Keywords: IRS2; Insulin receptor substrate; IRS1

Diabetic retinopathy is characterized by early onset of neuronal cell death. We previously showed that insulin mediates a prosurvival pathway in retinal neurons and normal retina expresses highly active basal receptor/Akt signaling stable throughout feeding fasting. Using the streptozotocin-induced diabetic rat model, we tested hypothesis diabetes diminishes receptor concomitantly with increased diabetes-induced apoptosis. The expression, phosphorylation status, and/or kinase activity downstream proteins were investigated retinas age-matched control, diabetic, insulin-treated rats. Four weeks reduced kinase, substrate (IRS)-1/2-associated phosphatidylinositol 3-kinase, Akt without altering or IRS-1/2 expression tyrosine phosphorylation. After 12 diabetes, constitutive autophosphorylation IRS-2 reduced, changes p42/p44 mitogen-activated protein IRS-1. Sustained systemic treatment rats prevented loss activity, acute intravitreal administration restored activity. Insulin receptor-beta maintained ex vivo, demonstrating functional receptors suggesting ligand as cause for These results demonstrate progressively impairs through suggests this survival may contribute to initial stages retinopathy.