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BioMed Research International
Volume 2014, Article ID 309151, 9 pages
http://dx.doi.org/10.1155/2014/309151
Research Article

Rosiglitazone Increases Cerebral Klotho Expression to Reverse Baroreflex in Type 1-Like Diabetic Rats

1Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
2Division of Nephrology, Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
3Department of Cardiology, Chi-Mei Medical Center, Yong Kang, Tainan 71004, Taiwan
4Department of Neurosurgery, Taipei Medical University-Shuang Ho Hospital, Taipei 23561, Taiwan

Received 4 November 2013; Accepted 7 January 2014; Published 13 February 2014

Academic Editor: Juei-Tang Cheng

Copyright © 2014 Li-Jen Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Reduced baroreflex sensitivity (BRS) is widely observed in diabetic human and animals. Rosiglitazone is one of the clinically used thiazolidinediones (TZD) known as PPARγ agonist. Additionally, the klotho protein produced from choroid plexus in the central nervous system is regulated by PPARγ. In an attempt to develop the new therapeutic strategy, we treated streptozotocin-induced diabetic rats (STZ) with rosiglitazone (STZ + TZD) orally at 10 mg/kg for 7 days. Also, STZ rats were subjected to intracerebroventricular (ICV) infusion of recombinant klotho at a dose of 3 μg/2.5 μL via syringe pump (8 μg/hr) daily for 7 days. The BRS and heart rate variability were then estimated under challenge with a depressor dose of sodium nitroprusside (50 μg/kg) or a pressor dose of phenylephrine (8 μg/kg) through an intravenous injection. Lower expression of klotho in medulla oblongata of diabetic rats was identified. Cerebral infusion of recombinant klotho or oral administration of rosiglitazone reversed BRS in diabetic rats. In conclusion, recovery of the decreased klotho in brain induced by rosiglitazone may restore the impaired BRS in diabetic rats. Thus, rosiglitazone is useful to reverse the reduced BRS through increasing cerebral klotho in diabetic disorders.