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Article

12-Lipoxygenase Inhibition on Microalbuminuria in Type-1 and Type-2 Diabetes Is Associated with Changes of Glomerular Angiotensin II Type 1 Receptor Related to Insulin Resistance

Department of Nephrology, the First Hospital of Jilin University, Changchun 130021, China
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Author to whom correspondence should be addressed.
Academic Editor: Lu Cai
Int. J. Mol. Sci. 2016, 17(5), 684; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17050684
Received: 29 March 2016 / Revised: 18 April 2016 / Accepted: 27 April 2016 / Published: 6 May 2016
(This article belongs to the Special Issue Diabetic Complications: Pathophysiology, Mechanisms, and Therapies)
(1) Background: 12-lipoxygenase (12-LO) is involved in the development of diabetic nephropathy (DN). In the present study, we investigated whether 12-LO inhibition may ameliorate type-2 DN (T2DN) by interfering with insulin resistance (IR); (2) Methods: Rat glomerular mesangial cells, glomeruli and skeletal muscles were isolated and used in this study. Kidney histological changes were confirmed by periodic-acid Schiff staining; mRNA expression was detected by competitive reverse transcription polymerase chain reaction; and the protein level was determined by Western blot and the enzyme-linked immunosorbent assay, respectively; (3) Results: The inhibition of 12-LO attenuated microalbuminuria (MAU) increases in type-2 diabetic rats, but not in type-1 diabetic rats. Infusion of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) significantly increased the expression of angiotensin II (Ang II) and Ang II type 1 receptor (AT1R), but decreased the expression of AT1R-associated protein (ATRAP) in rat glomeruli, compared to the control. An in vitro study revealed that both 12(S)-HETE and insulin upregulated AT1R expression in rat mesangial cells. In the presence of p38 mitogen-activated protein kinase (MAPK) inhibitor, SB202190, the 12(S)-HETE-induced ATRAP reduction was significantly abolished. Interestingly, 12-LO inhibition did not influence AT1R expression in type-1 diabetic rats, but significantly abolished the increased AT1R and Ang II expression in glomeruli of type-2 diabetic rats. Furthermore, the inhibition of 12-LO significantly corrected impaired insulin sensitivity and fast serum insulin level, as well as the p-AMP-activated protein kinase (AMPK) reduction in skeletal muscle of type-2 diabetic rats; (4) Conclusion: The inhibition of 12-LO potentially ameliorated MAU by preventing IR through the downregulation of glomerular AT1R expression in T2DN. View Full-Text
Keywords: 12-lipoxygenase; insulin resistance; angiotensin II type 1 receptor; diabetic nephropathy 12-lipoxygenase; insulin resistance; angiotensin II type 1 receptor; diabetic nephropathy
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MDPI and ACS Style

Xu, H.-Z.; Cheng, Y.-L.; Wang, W.-N.; Wu, H.; Zhang, Y.-Y.; Zang, C.-S.; Xu, Z.-G. 12-Lipoxygenase Inhibition on Microalbuminuria in Type-1 and Type-2 Diabetes Is Associated with Changes of Glomerular Angiotensin II Type 1 Receptor Related to Insulin Resistance. Int. J. Mol. Sci. 2016, 17, 684. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17050684

AMA Style

Xu H-Z, Cheng Y-L, Wang W-N, Wu H, Zhang Y-Y, Zang C-S, Xu Z-G. 12-Lipoxygenase Inhibition on Microalbuminuria in Type-1 and Type-2 Diabetes Is Associated with Changes of Glomerular Angiotensin II Type 1 Receptor Related to Insulin Resistance. International Journal of Molecular Sciences. 2016; 17(5):684. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17050684

Chicago/Turabian Style

Xu, Hong-Zhao, Yan-Li Cheng, Wan-Ning Wang, Hao Wu, Yuan-Yuan Zhang, Chong-Sen Zang, and Zhong-Gao Xu. 2016. "12-Lipoxygenase Inhibition on Microalbuminuria in Type-1 and Type-2 Diabetes Is Associated with Changes of Glomerular Angiotensin II Type 1 Receptor Related to Insulin Resistance" International Journal of Molecular Sciences 17, no. 5: 684. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17050684

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