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

Brian J. DeBosch, Elisabeth Baur, Baljit K. Deo, Miki Hiraoka, Arno K. Kumagai

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1157-1167
Number of pages11
JournalJournal of Neurochemistry
Volume77
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Diabetic retinopathy
  • GLUT1
  • Glucose transport
  • Inner blood-retinal barrier
  • Insulin-like growth factor
  • Retinal endothelial cells

Fingerprint

Dive into the research topics of 'Effects of insulin-like growth factor-1 on retinal endothelial cell glucose transport and proliferation'. Together they form a unique fingerprint.

Cite this