Exogenous 3-Deoxyglucosone-Induced Carbonyl and Oxidative Stress Causes β-Cells Dysfunction by Impairing Gut Permeability in Rats

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L. Zhou^1#, X. D. Song^1#, H. Xu¹, G. Q. Liang¹, F. Wang¹, L. R. Zhang¹, F. Huang¹, J. Cai¹, and G. R. Jiang^1,a*

¹Suzhou Academy of Wumen Chinese Medicine, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, China

^# These authors contributed equally to this work.

^* To whom correspondence should be addressed.

Received May 11, 2018; Revision received June 27, 2018

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3-Deoxyglucosone (3DG) is a highly reactive dicarbonyl species, and its accumulation evokes carbonyl and oxidative stress. Our recent data reveal the role of 3DG as an independent factor for the development of prediabetes and suggest that intestine could be its novel target tissue. The present study investigated whether exogenous 3DG increases intestinal permeability by triggering carbonyl and oxidative stress, thus contributing to β-cell dysfunction. Rats were administered 3DG for two weeks by gastric gavage. Then levels of insulin, ROS, MDA, SOD, NLRP3, TNF-α and IL-1β in blood plasma as well as the ROS level and content of TNF-α and IL-1β in pancreas were assessed. Also, the expression of E-cadherin and ZO-1 as well as levels of 3DG, protein carbonylation, ROS, TNF-α and IL-1β in colon were determined. The 3DG-treated rats showed an elevation in systemic oxidative stress (ROS, MDA and SOD) and in inflammation (TNF-α and IL-1β), decreased plasma insulin level 15 min after the glucose load, and increased levels of TNF-α, IL-1β and ROS in pancreatic tissue. In colon tissues of the 3DG-treated rats, decreased E-cadherin expression and increased ROS production as well as an elevation of TNF-α and IL-1β levels were observed. Interestingly, elevation of colon protein carbonylation was observed in the 3DG-treated rats that displayed 3DG deposition in colon tissues. We revealed for the first time that 3DG deposition in colon triggers carbonyl and oxidative stress and, as a consequence, impairs gut permeability. The enhanced intestinal permeability caused by 3DG deposition in colon results in systemic and pancreatic oxidative stress and inflammatory process, contributing to the development of β-cell dysfunction.

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KEY WORDS: 3-deoxyglucosone, prediabetes, intestinal permeability, carbonyl and oxidative stress, protein carbonylation, ROS, β-cell dysfunction

DOI: 10.1134/S0006297918110068

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