Hyperglycemia, a major cause of vascular complications in diabetes, has been shown to activate the diacylglycerol (DAG)-protein kinase C (PKC) pathway in vascular tissues. We have found that D-α-tocopherol (vitamin E) treatment reversed the adverse effects of hyperglycemia both in vitro and in vivo. In aortic smooth muscle cells (ASMCs), the PKC specific activity from the membranous fraction and total DAG were increased by 31 ± 4% (P < 0.05) and 50 ± 7% (P < 0.05), respectively, when the glucose levels were changed from 5.5 to 22 mmol/1. D-α-tocopherol prevented the glucose-stimulated increases in DAG level and PKC activity as well as the amount of PKC βII isoform in ASMCs cultured with elevated glucose levels. Comparing streptozotocin-induced diabetic rats after 2 weeks of disease to controls, specific membranous PKC activities and total DAG levels were increased in aorta (162%, P < 0.05; 60%, P < 0.05). Intraperitoneal injection of D-α-tocopherol (40 mg/kg) every other day resulted in a significant decrease of the elevated membranous PKC specific activity and total DAG levels in parallel with a significant increase of D-α-tocopherol content in the aorta. These findings suggested that D-α-tocopherol can prevent the activation of PKC in the vascular cells and aorta induced by hyperglycemia by normalizing the elevated levels of DAG.
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VASCULAR DYSFUNCTION IN DIABETES—ENDOTHELIAL AND SMOOTH MUSCLE CELLS|
July 01 1996
Vitamin E Normalizes Diacylglycerol—Protein Kinase C Activation Induced by Hyperglycemia in Rat Vascular Tissues
Makoto Kunisaki;
Makoto Kunisaki
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School
Boston, Massachusetts
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University
Fukuoka, Japan
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Umeda Fumio;
Umeda Fumio
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University
Fukuoka, Japan
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Hajime Nawata;
Hajime Nawata
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University
Fukuoka, Japan
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George L King
George L King
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School
Boston, Massachusetts
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Address correspondence and reprint requests to Dr. George L. King, Joslin Diabetes Center, Research Division, One Joslin Place, Boston, MA 02215
Diabetes 1996;45(Supplement_3):S117–S119
Article history
Accepted:
September 26 1995
PubMed:
8674876
Citation
Makoto Kunisaki, Umeda Fumio, Hajime Nawata, George L King; Vitamin E Normalizes Diacylglycerol—Protein Kinase C Activation Induced by Hyperglycemia in Rat Vascular Tissues. Diabetes 1 July 1996; 45 (Supplement_3): S117–S119. https://doi.org/10.2337/diab.45.3.S117
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