期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 375, 期 1-2, 页码 89-96出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2013.04.027
关键词
Hyperuricemia; Pancreatic beta-cell; Oxidative stress; AMPK; ERK
资金
- National Natural Science Foundation of China [81070673, 81172263]
- Special Foundation of Guangdong Province College Talent Introduction [10027425]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry [20111568]
Hyperuricaemia is a disorder of purine metabolism, and is strongly associated with insulin resistance and abnormal glucose metabolism. As the producer of insulin, pancreatic beta cells might be affected by elevated serum uric acid levels and contribute to the disregulated glucose metabolism. In this study, we investigated the effect of high uric acid on rat pancreatic beta cell function. Under high uric acid condition, proliferation of pancreatic beta cells was inhibited, production of reactive oxygen species increased, and glucose stimulated insulin secretion was also compromised. Further examination on signal transduction pathways revealed that uric acid-induced ROS is involved in the activation of adenosine monophosphate-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK). Pharmacological inhibition of ERK activation rescued beta cells from growth inhibition. More importantly, activation of ERK induced by uric acid is significantly diminished by AMPK inhibitor, indicating ERK as a downstream target of AMPK in response to high uric acid condition. We also investigated the transportation channel for uric acid into pancreatic beta cells. While major urate transporter URAT1 is not expressed in beta cells, organic anion transporter (OAT) inhibitor successfully blocked the activation of ERK by uric acid. Our data indicate that high uric acid levels induce oxidative damage and inhibit growth of rat pancreatic beta cells by activating the AMPK and ERK signal pathways. Hyperuricemia may contribute to abnormal glucose metabolism by causing oxidative damage and function inhibition of pancreatic beta cells. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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