TY - JOUR
T1 - Effects of insulin-like growth factor-1 on retinal endothelial cell glucose transport and proliferation
AU - DeBosch, Brian J.
AU - Baur, Elisabeth
AU - Deo, Baljit K.
AU - Hiraoka, Miki
AU - Kumagai, Arno K.
PY - 2001
Y1 - 2001
N2 - 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 (Pl3 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.
AB - 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 (Pl3 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.
KW - Diabetic retinopathy
KW - GLUT1
KW - Glucose transport
KW - Inner blood-retinal barrier
KW - Insulin-like growth factor
KW - Retinal endothelial cells
UR - http://www.scopus.com/inward/record.url?scp=0034999443&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.2001.00325.x
DO - 10.1046/j.1471-4159.2001.00325.x
M3 - Article
C2 - 11359881
AN - SCOPUS:0034999443
SN - 0022-3042
VL - 77
SP - 1157
EP - 1167
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 4
ER -