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Effects of insulin‐like growth factor‐1 on retinal endothelial cell glucose transport and proliferation
Author(s) -
DeBosch Brian J.,
Baur Elisabeth,
Deo Baljit K.,
Hiraoka Miki,
Kumagai Arno K.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00325.x
Subject(s) - protein kinase c , endocrinology , medicine , biology , growth factor , glucose transporter , retina , retinal , signal transduction , glut1 , microbiology and biotechnology , insulin , biochemistry , receptor , neuroscience
Insulin‐like growth factor‐1 (IGF‐1) plays important roles in the developing and mature retina and in pathological states characterized by retinal neovascularization, such as diabetic retinopathy. The effects of IGF‐1 on glucose transport and proliferation and the signal transduction pathways underlying these effects were studied in a primary bovine retinal endothelial cell (BREC) culture model. IGF‐1 stimulated uptake of the glucose analog 2‐deoxyglucose in a dose‐dependent manner, with a maximal uptake at 25 ng/mL (3.3 n m ) after 24 h. Increased transport occurred in the absence of an increase in total cellular GLUT1 transcript or protein. IGF‐1 stimulated activity of both protein kinase C (PKC) and phosphatidylinositol‐3 kinase (PI3 kinase), and both pathways were required for IGF‐1‐mediated BREC glucose transport and thymidine incorporation. Use of a selective inhibitor of the β isoform of PKC, LY379196, revealed that IGF‐1 stimulation of glucose transport was mediated by PKC‐β; however, inhibition of PKC‐β had no effect on BREC proliferation. Taken together, these data suggest that the actions of IGF‐1 in retinal endothelial cells couple proliferation with delivery of glucose, an essential metabolic substrate. The present studies extend our general understanding of the effects of IGF‐1 on vital cellular activities within the retina in normal physiology and in pathological states such as diabetic retinopathy.