differential roles of hyperglycemia and hypoinsulinemia in diabetes induced retinal cell death evidence for retinal insulin resistance微分作用的高血糖和hypoinsulinemia糖尿病引起的视网膜细胞死亡的证据视网膜胰岛素抵抗.pdfVIP

Differential Roles of Hyperglycemia and Hypoinsulinemia in Diabetes Induced Retinal Cell Death: Evidence for Retinal Insulin Resistance 1 1 2¤a 2 2¤b Patrice E. Fort *, Mandy K. Losiewicz , Chad E. N. Reiter , Ravi S. J. Singh , Makoto Nakamura , 1 2 1 Steven F. Abcouwer , Alistair J. Barber , Thomas W. Gardner 1 Kellogg Eye Center, University of Michigan, Ophthalmology and Visual Sciences Department, Ann Arbor, Michigan, United States of America, 2 Department of Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania, United States of America Abstract Diabetes pathology derives from the combination of hyperglycemia and hypoinsulinemia or insulin resistance leading to diabetic complications including diabetic neuropathy, nephropathy and retinopathy. Diabetic retinopathy is characterized by numerous retinal defects affecting the vasculature and the neuro-retina, but the relative contributions of the loss of retinal insulin signaling and hyperglycemia have never been directly compared. In this study we tested the hypothesis that increased retinal insulin signaling and glycemic normalization would exert differential effects on retinal cell survival and retinal physiology during diabetes. We have demonstrated in this study that both subconjunctival insulin administration and systemic glycemic reduction using the sodium-glucose linked transporter inhibitor phloridzin affected the regulation of retinal cell survival in diabetic rats. Both treatments partially restored the retinal insulin signaling without increasing plasma insulin levels. Retinal tr