title: Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway.
abstract: 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)
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kunisaki
authors.forename: S E
authors.initials: SE
authors.lastname: Bursell
authors.forename: A C
authors.initials: AC
authors.lastname: Clermont
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: L M
authors.initials: LM
authors.lastname: Ballas
authors.forename: M R
authors.initials: MR
authors.lastname: Jirousek
authors.forename: F
authors.initials: F
authors.lastname: Umeda
authors.forename: H
authors.initials: H
authors.lastname: Nawata
authors.forename: G L
authors.initials: GL
authors.lastname: King
mesh_terms: 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*
chemical_list: D004075:Diglycerides; D007527:Isoenzymes; D010168:Palmitates; D014810:Vitamin E; D011493:Protein Kinase C