Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway

Am J Physiol. 1995 Aug;269(2 Pt 1):E239-46. doi: 10.1152/ajpendo.1995.269.2.E239.


We have characterized effects of d-alpha-tocopherol (vitamin E) on activation of protein kinase C (PKC) and diacylglycerol (DAG) levels in retinal tissues of diabetic rats and correlated its effects to diabetes-induced changes in retinal hemodynamics. Membrane PKC specific activities were increased by 71% in streptozocin-induced diabetic rats compared with controls (P < 0.05). Western blot analysis showed that membrane PKC-beta II was increased by 133 +/- 5% (P < 0.05). Injection of d-alpha-tocopherol (40 mg/kg ip) every other day prevented the increases in membrane PKC specific activity and PKC-beta II protein by immunoblots. Diabetes-induced increases in DAG levels were also normalized by d-alpha-tocopherol treatment of 2 wk duration. Physiologically, angiographic abnormalities of retinal hemodynamics based on computerized video-based fluorescein angiography and associated with increases of DAG and membranous PKC levels were also prevented by d-alpha-tocopherol treatment in diabetic rats. The effect of d-alpha-tocopherol on retinal vascular cells was also studied. Exposure of retinal endothelial cells to 22 mM glucose for 3 days increased total DAG and [3H]palmitate-labeled DAG levels by 35 +/- 8 and 50 +/- 8% (P < 0.05), respectively, compared with exposure to 5.5 mM glucose. The presence of d-alpha-tocopherol (50 micrograms/ml) prevented the increases in total DAG and [3H]palmitate-labeled DAG levels in cells exposed to 22 mM glucose. These findings suggested that treatment with d-alpha-tocopherol can prevent diabetes-induced abnormalities in rat retinal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diglycerides / metabolism*
  • Endothelium / cytology
  • Endothelium / metabolism
  • Isoenzymes / metabolism
  • Male
  • Palmitates / metabolism
  • Protein Kinase C / metabolism*
  • Rats
  • Regional Blood Flow
  • Retina / metabolism
  • Retinal Vessels / drug effects*
  • Retinal Vessels / physiopathology*
  • Vitamin E / blood
  • Vitamin E / metabolism
  • Vitamin E / pharmacology*


  • Diglycerides
  • Isoenzymes
  • Palmitates
  • Vitamin E
  • Protein Kinase C