Vitamin e treatment prevents diabetes-induced abnormality in
retinal blood flow possibly through the diacylglycerol-protein kinase
c pathway.
Kunisaki, Makoto, Sven-Erik Bursell, Allen C. Clermont, Hidehiro
Ishii, Lawrence M. Ballas, Michael R. Jirousek, Fumio Umeda, Hajime
Nawata, and George L. King.
Research Division, Joslin Diabetes Center, and Departments of
Medicine, Brigham and Women's Hospital and Harvard Medical School,
Boston, MA 02215, Third Department of Internal Medicine, Faculty of
Medicine, Kyushu University, Fukuoka 812, Japan, Sphinx
Pharmaceuticals Corporation, Durham, NC 27717, and Lilly Research
Laboratories, Inc., Indianapolis, IN 46285
APStracts 2:0040E, 1995.
We have characterized the effects of d-[alpha]-tocopherol (vitamin E)
on the 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.
Comparing streptozotocin-induced diabetic rats to controls, membrane
PKC specific activities were increased by 71% (P<0.05). Western
blot analysis showed membrane PKC [beta]II isoform was increased by
133+45% (P<0.05). Intraperitoneal injection of d-[alpha]-tocopherol
(40 mg/kg) 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 weeks duration. Physiologically,
angiographic abnormalities of retinal hemodynamics based on
computerized video based fluorescein angiography and assoicated 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 (REC) to 22 mM glucose for
three days compared to 5 mM glucose, increased total DAG and [3H]
-palmitate labeled DAG levels by 35%+8% and 50+8% (P<0.05),
respectively, more than REC exposed to 5.5 mM glucose. The presence
of d-[alpha]-tocopherol (50[mu]g/ml) prevented the increases in both
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. The mechanism of the d-[alpha]-tocopherol's
effect appears to be mediated by the normalization of hyperglycemia
-induced activation of DAG-PKC pathway in the retina of diabetic rats.
Received 18 August 1994; accepted in final form 27 February 1995.
APS Manuscript Number E334-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 March 1995.