Glucose Dilates Renal Afferent Arterioles via Glucose Transporter-1
Document Type
Article
Publication Date
2018
Keywords
afferent arteriole, nitric oxide
Digital Object Identifier (DOI)
https://doi.org/10.1152/ajprenal.00409.2017
Abstract
Glomerular hyperfiltration occurs during the early stage of diabetes. An acute glucose infusion increases glomerular filtration rate. The involvement of tubuloglomerular feedback response and direct effect of glucose on the afferent arterioles (Af-Arts) have been suggested. However, the signaling pathways to trigger Af-Art dilatation have not been fully identified. Therefore, in the present study we tested our hypothesis that an increase in glucose concentration enhances endothelial nitric oxide synthesis activity and dilates the Af-Arts via glucose transporter-1 (GLUT1) using isolated mouse Af-Arts with perfusion. We isolated and microperfused the Af-Arts from nondiabetic C57BL/6 mice. The Af-Arts were preconstricted with norepinephrine (1 µM). When we switched the d-glucose concentration from low (5 mM) to high (30 mM) in the perfusate, the preconstricted Af-Arts significantly dilated by 37.8 ± 7.1%, but L-glucose did not trigger the dilation. GLUT1 mRNA was identified in microdisserted Af-Arts measured by RT-PCR. Changes in nitric oxide (NO) production in Af-Art were also measured using fluorescent probe when ambient glucose concentration was increased. When the d-glucose concentration was switched from 5 to 30 mM, NO generation in Af-Art was significantly increased by 19.2 ± 6.2% (84.7 ± 4.1 to 101.0 ± 9.3 U/min). l-Glucose had no effect on the NO generation. The GLUT1-selective antagonist 4-[({[4-(1,1-Dimethylethyl)phenyl]sulfonyl}amino)methyl]-N-3-pyridinylbenzamide and the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester blocked the high glucose-induced NO generation and vasodilation. In conclusion, we demonstrated that an increase in glucose concentration dilates the Af-Art by stimulation of the endothelium-derived NO production mediated by GLUT1.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
American Journal of Physiology-Renal Physiology, v. 315, issue 1, p. F123-F129
Scholar Commons Citation
Zhang, Jie; Jiang, Shan; Wei, Jin; Yip, Kay-Pong; Wang, Lei; Lai, En Yin; and Liu, Ruisheng, "Glucose Dilates Renal Afferent Arterioles via Glucose Transporter-1" (2018). Molecular Pharmacology & Physiology Faculty Publications. 26.
https://digitalcommons.usf.edu/mpp_facpub/26
