Effects of insulin-like growth factor-1 on retinal endothelial cell glucose transport and proliferation

Insulin-like growth factor-1 (IGF-1) plays important roles in the developin g and mature retina and in pathological states characterized by retinal neo vascularization, such as diabetic retinopathy. The effects of IGF-1 on gluc ose transport and proliferation and the signal transduction pathways underl ying these effects were studied in a primary bovine retinal endothelial cel l (BREC) culture model. IGF-1 stimulated uptake of the glucose analog 2-deo xyglucose in a dose-dependent manner, with a maximal uptake at 25 ng/mL (3. 3 nM) after 24 h. Increased transport occurred in the absence of an increas e in total cellular GLUT1 transcript or protein. IGF-1 stimulated activity of both protein kinase C (PKC) and phosphatidylinositol-3 kinase (PI3 kinas e), and both pathways were required for IGf-1-mediated BREC glucose transpo rt and thymidine incorporation. selective inhibitor of the beta isoform of PKC, LY379196, revealed that IGF-1 stimulation of glucose transport was med iated by PKC-beta; however. inhibition of PKC-beta had no effect on BREC pr oliferation. Taken together, these data suggest that the actions of IGF-1 i n retinal endothelial cells couple proliferation with delivery of glucose, an essential metabolic substrate. The present studies extend our general un derstanding of the effects of IGF-1 on vital cellular activities within the retina in normal physiology and in pathological states such as diabetic re tinopathy.