美国医学专业作业-Plasma IKK NF-kB [5]
论文作者:www.51lunwen.org论文属性:作业 Assignment登出时间:2014-06-01编辑:lzm点击率:10775
论文字数:2840论文编号:org201406012014576248语种:英语 English地区:中国价格:免费论文
关键词:美国医学专业Plasma IKK NF-kB血浆游离脂肪酸free plasma fatty acidsreactive oxygen species
摘要:This study examines the effect of prolonged exposure to FFA on the NF-kB activated inflammatory pathway. In vivo, infusion of oleate impaired insulin secretion as measured by c-peptide, while olive oil did not impair insulin secretion but impaired insulin sensitivity.
nfusion of salicylate with olive oil prevented the decrease in sensitivity index. Salicylate alone had no effect on insulin sensitivity. In vivo β-cell compensates for insulin resistance by increasing insulin secretion. The disposition index calculated as the sensitivity index multiplied by c-peptide level is conventionally used as an index of β-cell function. When disposition index was used to correct for β-cell sensitivity, both oleate infusion and olive oil infusion resulted in a decrease in DI compared with saline (Figure 6a, 6b). This is consistent with the reduced β-cell function caused by oleate or olive oil. The infusion of salicylate restored the disposition index. Salicylate alone had no effect on the disposition index.
Figure 5. Sensitivity Index (M/I = GINF/Insulin) during the hyperglycemic clamp in 12 week old normal female Wistar rats treated for 48h with an i.v. infusion of: A) 1) Saline alone (SAL n=12), 2) Oleate alone (OLE 1.3µEq·min-1 n=10), 3) Oleate + Salicylate (OLE+SLY, oleate-1.3µEq·min-1, SLY-0.117mg·kg-1min-1, n=8), 4) Salicylate alone, (SLY, n=9); B) 1) Saline alone (SAL n=12), 2) Olive oil alone (OLO 5µl·min-1 n=7), 3) Olive oil + Salicylate (OLO+SLY, olive oil-5µl·min-1, SLY-0.117mg·kg-1min-1, n=11), 4) Salicylate alone, (SLY, n=9); Data are means ± SE.
Figure 6. Disposition Index (DI = M/I x C-peptide, index of β-cell function) during the hyperglycemic clamp in 12 week old normal female Wistar rats treated for 48h with an i.v. infusion of: A) 1) Saline alone (SAL n=12), 2) Oleate alone (OLE 1.3µEq·min-1 n=10), 3) Oleate + Salicylate (OLE+SLY, oleate-1.3µEq·min-1, SLY-0.117mg·kg-1min-1, n=8), 4) Salicylate alone, (SLY, n=9); B) 1) Saline alone (SAL n=12), 2) Olive oil alone (OLO 5µl·min-1 n=7), 3) Olive oil + Salicylate (OLO+SLY, olive oil-5µl·min-1, SLY-0.117mg·kg-1min-1, n=11), 4) Salicylate alone, (SLY, n=9); Data are means ± SE.
Discussion:
This study examines the effect of prolonged exposure to FFA on the NF-kB activated inflammatory pathway. In vivo, infusion of oleate impaired insulin secretion as measured by c-peptide, while olive oil did not impair insulin secretion but impaired insulin sensitivity. This would suggest that different fat impair β-cell function through different mechanisms. However, the effect of oleate and olive oil were prevented by the co-infusion of salicylate. Salicylate is a weak inhibitor of IKK. The infusion of salicylate with oleate prevented the reduction in insulin secretion caused by oleate. The co-infusion of salicylate with olive oil also prevented the reduction in insulin resistance. In this study a two-step hyperglycemic clamp was used to calculate insulin sensitivity, however the gold standard for determining insulin sensitivity is the hyperinsulinemic-euglycemic clamp. A hyperinsulinemic-euglycemic should also be performed to validate the effects of olive oil. Despite this, the study demonstrates that even though oleate and olive oil are different types of fat which negatively affect different aspects of β-cell functions, both are mediated by the IKK/NF-kB activated pathway. Ex-vivo and in vitro data show similar results. Salicylate was shown in both cases to prevent the effect of oleate and olive oil on insulin secretion and insulin sensitivity. In a proof of mechanism study, Dr. Fong of Prince Edward Island University
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