Diabetes & Metabolism Journal

Original Articles

Oxidative Stress Causes Vascular Insulin Resistance in OLETF Rat Through Increased IRS-1 Degradation.: Jung Lae Park, Young Sil Lee, Bo Hyun Kim, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son; Korean Diabetes J. 2007;31(1):22-32. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.22

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BACKGROUND
Insulin resistance and oxidative stress have been reported to play essential pathophysiological roles in diabetic cardiovascular complication. The relationship between insulin resistance and oxidative stress in vasculature remains unclear. The study was conducted to assess whether oxidative stress induce vascular insulin resistance in OLETF rat, a model of type 2 diabetes METHODS: We used OLETF rats (20/30/40 weeks, n = 5/5/5), as models of type 2 DM, and LETO rats (20/30/40 weeks, n = 5/5/5) as controls. Aortas of each rats were extracted. Superoxide anion production was detected by NBT assay and lucigenin assay. 8-hydroxyguanosine (OHdG) and nitrotyrosine were detected as markers of oxidative stress in 20 and 40 weeks groups. The glucose uptake of aortas was measured by detecting 2-deoxyglucose uptake in both groups. The expression of IR, IRS-1, PI3-K and Akt/PKB were detected by immuno precipitation and immunoblotting in 20, 30 and 40 weeks groups RESULTS: Superoxide anion production and markers of oxidative stress (8-OHdG, nitrotyrosine) were significantly increased in aortas of OLETF rats compared with controls. Aortas of OLETF rats exhibited decreased IRS-1 content and increased phosphorylation of IRS-1 at Ser307 compared with LETO rats. There were no significant differences in expressions of IR, PI3-K and Akt/PKB between two groups CONCLUSION: These results suggest that oxidative stress induces insulin resistance in vasculature of OLETF rat specifically through increasing serine phosphorylation of IRS-1 and its degradation by a proteasome-dependent pathway, providing an alternative mechanism that may explain the association with insulin resistance and diabetic vascular complications.

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Anti-diabetic effects of benfotiamine on an animal model of type 2 diabetes mellitus
Kang Min Chung, Wonyoung Kang, Dong Geon Kim, Hyun Ju Hong, Youngjae Lee, Chang-Hoon Han
Korean Journal of Veterinary Research.2014; 54(1): 21. CrossRef

Lipopolysaccharide-Induced Changes in Vascular Reactivity of Diabetic Rat Aorta.: Ye Kyung Seo, Sang Won Chung, Jik Hwa Nam, Byoung Ho Sin, Dong Hee Kim, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim; Korean Diabetes J. 1997;21(3):280-288. Published online January 1, 2001

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Abstract PDF: Backgound: Hemodynamic deteriorations in diabetes mellitus may be mediated by increased contractile response to catecholamines and/or by decreased relaxative response to vasodilators such as acetylcholine(Ach). Decrease in peripheral vascular reactivity to vasoconstrictor was known to be an ominous sign that happens during sepsis or after injection of bacterial lipopolysaccharides(LPS). In this study, we compared the effects of LPS on function of diabetic rat aorta with impaired vascular reactivity with those of control rat aorta. METHODS: Contractile responses to cumulative concentrations(10'M to 3X10'M) of norepinephrine (NE) were measured in aorta isolated ftom the control and 4 to 5-week streptozotocin-induced diabetic rat at 6 hours after LPS treatment to compare with contractile responses of untreated group. We measured relaxative responses to cumulative concentrations(10'M to 10M) of Ach and nitroprusside (NTP) in these aortas contracted submaximally by NE. RESULTS: Diabetic rat aortas showed significantly more impairment in relaxative responses to Ach than control rat aortas before LPS treatment(p0.05 = 0.0l). LPS treatment in those diabetic rat aortas decreased contractile responses to NE by 26.6%(p < 0.01); the changes were sirnilar to those of control (30.9%, p0.01). Relaxative responses to Ach were also significantly decreased by 25.0%(p 0.01) after L.PS treatment; the changes were similar to those of control(34.1%, p0.01). However relaxative responses to NTP were not changed in control and d.iabetic rat aortas by LPS treatment. CONCLUSION: These results suggest that diabetes may induce impairment in endothelium-dependent vascular relaxation and there rnay be no difference of L,P,S-induced effects on hemodynamic deterioration between 4 to 5-week diabetic and control rats.

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