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 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 nM) 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 beta isoform of PKC, LY379196, revealed that IGF-1 stimulation of glucose transport was mediated by PKC-beta; however, inhibition of PKC-beta 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.
DeBosch
B J
BJ
Department of Internal Medicine, Michigan Diabetes Research and Training Center, Ann Arbor, Michigan, USA.
Baur
E
E
Deo
B K
BK
Hiraoka
M
M
Kumagai
A K
AK
D019325:3-O-Methylglucose / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D007211:Indoles / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism
D004791:Enzyme Inhibitors; D051272:Glucose Transporter Type 1; D007211:Indoles; D008301:Maleimides; D009004:Monosaccharide Transport Proteins; D019325:3-O-Methylglucose; D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D005947:Glucose; C070515:bisindolylmaleimide I; D013936:Thymidine