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Am J Physiol Endocrinol Metab 269: E239-E246, 1995;
0193-1849/95 $5.00
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AJP - Endocrinology and Metabolism, Vol 269, Issue 2 E239-E246, Copyright © 1995 by American Physiological Society

ARTICLES

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

M. Kunisaki, S. E. Bursell, A. C. Clermont, H. Ishii, L. M. Ballas, M. R. Jirousek, F. Umeda, H. Nawata and G. L. King
Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.

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)


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