Interactions between vitamin E and glucose on B-cell functions in the rat: an in vivo and in vitro study.
Hyperglycemia exerts negative effects on B-cell functions that may involve oxidative stress. This was tested for by investigating effects of D-alpha-tocopherol (vitamin E), known as a free radical scavenger, on B-cell functions. For in vivo testing, rat pancreatic islets were transplanted syngeneically under the kidney capsule in streptozotocin-induced diabetic rats. Transplanted rats were treated with D-alpha-tocopherol (40 mg/kg, intraperitoneally injected every other day) or soybean oil for 2 or 6 weeks. Graft-bearing kidneys were then perfused and insulin release was measured after stimulation sequentially with glucose (27 mmol/L) and L-arginine (10 mmol/L). D-alpha-tocopherol treatment for 2 or 6 weeks failed to restore glucose-induced insulin secretion, whereas treatment for 2 but not for 6 weeks enhanced basal insulin release (by 24%, p < 0.05) and arginine-induced release (by 79%, p < 0.05). Treatment did not affect graft content of preproinsulin mRNA. The presence of D-alpha-tocopherol (50 microg/ml) in vitro enhanced glucose (27 mmol/L)-stimulated insulin release from batch-type incubated islets by 33% (p < 0.05). Exposing islets to D-alpha-tocopherol for 1 day in the presence of 38 mmol/L glucose enhanced glucose-stimulated insulin release (by 25%, p < 0.05), L-arginine-stimulated release (by 37%, p < 0.05) and elevated islet insulin content (by 20%, p < 0.05). These effects of exposure to D-alpha tocopherol were lost when the culture period was extended up to 3 weeks. It is concluded that D-alpha-tocopherol exerts moderate beneficial effects on B-cell functions during short to intermediate length of high glucose exposure. These effects are, however, insufficient to support a major role for oxidative stress behind glucotoxicity toward B cells.
Tajiri
Y
Y
Department of Molecular Medicine, Karolinska Institute and Hospital, Stockholm, Sweden.
Grill
V E
VE
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D004347:Drug Interactions; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D007668:Kidney; D008297:Male; D011384:Proinsulin / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011920:Rats, Inbred WF; D017208:Rats, Wistar; D016042:Transplantation, Heterotopic; D014810:Vitamin E / Q000494:pharmacology*
D007328:Insulin; D011498:Protein Precursors; D012333:RNA, Messenger; D014810:Vitamin E; C013737:preproinsulin; D012313:RNA; D011384:Proinsulin; D001120:Arginine; D005947:Glucose