Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway.
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)
Kunisaki
M
M
Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Bursell
S E
SE
Clermont
A C
AC
Ishii
H
H
Ballas
L M
LM
Jirousek
M R
MR
Umeda
F
F
Nawata
H
H
King
G L
GL
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004075:Diglycerides / Q000378:metabolism*; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010168:Palmitates / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D012039:Regional Blood Flow; D012160:Retina / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects* / Q000503:physiopathology*; D014810:Vitamin E / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*
D004075:Diglycerides; D007527:Isoenzymes; D010168:Palmitates; D014810:Vitamin E; D011493:Protein Kinase C