Abstract
Both insulin and IGF-1 have been implicated in control of retinal endothelial cell growth, neovascularization, and diabetic retinopathy. To precisely define the role of insulin and IGF-1 signaling in endothelium in these processes, we have used the oxygen-induced retinopathy model to study mice with a vascular endothelial cell-specific knockout of the insulin receptor (VENIRKO) or IGF-1 receptor (VENIFARKO). Following relative hypoxia, VENIRKO mice show a 57% decrease in retinal neovascularization as compared with controls. This is associated with a blunted rise in VEGF, eNOS, and endothelin-1. By contrast, VENIFARKO mice show only a 34% reduction in neovascularization and a very modest reduction in mediator generation. These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process.
Publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Animals
- Diabetic Retinopathy / etiology
- Diabetic Retinopathy / pathology
- Diabetic Retinopathy / physiopathology
- Diabetic Retinopathy / prevention & control*
- Disease Models, Animal
- Endothelial Growth Factors / physiology
- Endothelin-1 / physiology
- Endothelium, Vascular / pathology
- Endothelium, Vascular / physiopathology
- Humans
- Hypoxia / pathology
- Hypoxia / physiopathology
- Insulin / physiology
- Intercellular Signaling Peptides and Proteins / physiology
- Lymphokines / physiology
- Mice
- Mice, Inbred C57BL
- Mice, Inbred DBA
- Mice, Knockout
- Neovascularization, Pathologic*
- Nitric Oxide Synthase / physiology
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
- Receptor, IGF Type 1 / deficiency*
- Receptor, IGF Type 1 / genetics
- Receptor, IGF Type 1 / physiology
- Receptor, Insulin / deficiency*
- Receptor, Insulin / genetics
- Receptor, Insulin / physiology
- Retinal Vessels / pathology*
- Signal Transduction
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
Substances
- Endothelial Growth Factors
- Endothelin-1
- Insulin
- Intercellular Signaling Peptides and Proteins
- Lymphokines
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- NOS3 protein, human
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
- Nos3 protein, mouse
- Receptor, IGF Type 1
- Receptor, Insulin