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

2,459 View
19 Download
1 Crossref

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.

Citations

Citations to this article as recorded by

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

Effect of Overexpression of Gi Proteins on Insulin Actions in 3T3-L1 Adipocytes.: Hyun Shik Son, Bong Yun Cha, Sung Dae Moon, Jung Min Lee, Ok Ki Hong, Sang Ah Chang, Yu Bae Ahn, Kun Ho Yoon, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2000;24(4):404-412. Published online January 1, 2001

1,179 View
18 Download

Abstract PDF: BACKGROUND
It has been reported that G proteins are involved in biological actions of insulin. Especially, Gi protein is more associated with insulin actions than Gs proteins. Gi protein has at least three different subtypes of Gi 1, Gi 2 and Gi 3 protein. However, it is not certain which subtypes of Gi proteins are associated with biological actions of insulin. METHODS: To investigate which subtypes of Gi proteins are associated with insulin action, we overexpressed three different kinds of Gi protein, Gi 1, Gi 2 and Gi 3 protein, in 3T3-L1 adipocytes using DNA-polylysine-adenovirus complex transfection method. After incubating for 2 hours, 3T3-L1 adipocytes were treated with 100 nM insulin for the evaluation of biological actions of insulin. Moreover, to elucidate insulin stimulated insulin receptor autophosphorylation and IRS-1 phosphorylation, 3T3-L1 adipocytes were stimulated with 100 nM insulin for 10 minutes, homogenized and immunoprecipitated with anti-phosphotyrosine antibody. RESULTS: Transfection with Gi 2 gene resulted in increment in insulin-stimulated [3H]2-deoxyglucose (DOG) uptake without affecting basal 2-DOG uptake, but not with Gi 1 and Gi 3 gene transfection. There was unchanged glycogen synthesis rate in all three Gialphasubtypes. Insulin-induced increments of insulin receptor autophos phorylation and IRS-1 phosphorylation were found in Gi 2 protein overexpressed group, only. CONCLUSION: These results suggest that Gi 2 protein may be associated with regulation of biological actions of insulin.

First
Prev
Page of 1
Next
Last

Search