Differential roles of hyperglycemia and hypoinsulinemia in diabetes induced retinal cell death: evidence for retinal insulin resistance

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...

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Veröffentlicht in:PloS one 2011-10, Vol.6 (10), p.e26498-e26498
Hauptverfasser: Fort, Patrice E, Losiewicz, Mandy K, Reiter, Chad E N, Singh, Ravi S J, Nakamura, Makoto, Abcouwer, Steven F, Barber, Alistair J, Gardner, Thomas W
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container_issue 10
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container_title PloS one
container_volume 6
creator Fort, Patrice E
Losiewicz, Mandy K
Reiter, Chad E N
Singh, Ravi S J
Nakamura, Makoto
Abcouwer, Steven F
Barber, Alistair J
Gardner, Thomas W
description 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 transcriptomic and histological analysis also clearly demonstrated that local administration of insulin and systemic glycemia normalization use different pathways to counteract the effects of diabetes on the retina. While local insulin primarily affected inflammation-associated pathways, systemic glycemic control affected pathways involved in the regulation of cell signaling and metabolism. These results suggest that hyperglycemia induces resistance to growth factor action in the retina and clearly demonstrate that both restoration of glycemic control and retinal insulin signaling can act through different pathways to both normalize diabetes-induced retinal abnormality and prevent vision loss.
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These results suggest that hyperglycemia induces resistance to growth factor action in the retina and clearly demonstrate that both restoration of glycemic control and retinal insulin signaling can act through different pathways to both normalize diabetes-induced retinal abnormality and prevent vision loss.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22046295</pmid><doi>10.1371/journal.pone.0026498</doi><tpages>e26498</tpages><oa>free_for_read</oa></addata></record>
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subjects Analysis
Animals
Apoptosis
Biochemistry
Biology
Blood glucose
Cell Death
Cell survival
Complications
Complications and side effects
Control
Diabetes mellitus
Diabetes Mellitus - physiopathology
Diabetic neuropathies
Diabetic neuropathy
Diabetic retinopathy
Diabetic Retinopathy - pathology
Glucose
Glucose transporter
Hyperglycemia
Hyperglycemia - physiopathology
Insulin
Insulin - metabolism
Insulin - pharmacology
Insulin Resistance
Kinases
Medicine
Metabolism
Nephropathy
Neuropathy
Phlorhizin - pharmacology
Rats
Resistance factors
Restoration
Retina
Retina - pathology
Retinopathy
Rodents
Signal Transduction
Signaling
Sodium
Survival
title Differential roles of hyperglycemia and hypoinsulinemia in diabetes induced retinal cell death: evidence for retinal insulin resistance
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