Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway
| Autor: | Hidehiro Ishii, George L. King, H. Nawata, S E Bursell, F. Umeda, Makoto Kunisaki, M. R. Jirousek, Allen C. Clermont, L. M. Ballas |
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| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Palmitates Hemodynamics Biology Retina Diabetes Mellitus Experimental Diglycerides chemistry.chemical_compound Western blot Physiology (medical) Internal medicine medicine Animals Vitamin E Endothelium Diglyceride Protein Kinase C Protein kinase C Diacylglycerol kinase medicine.diagnostic_test Retinal Vessels Retinal Rats Isoenzymes Endocrinology medicine.anatomical_structure chemistry Regional Blood Flow lipids (amino acids peptides and proteins) |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 269:E239-E246 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | 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) |
| Databáze: | OpenAIRE |
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