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Experimental Diabetes Research
Volume 2012, Article ID 429020, 16 pages
http://dx.doi.org/10.1155/2012/429020
Research Article

Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin

1Department of Pharmacology and Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 280 South Chong Qing Road, Shanghai 200025, China
2Department of Pharmacology, Kinki University School of Medicine, Osaka 589-8511, Japan
3Division of New Drug Research, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
4Clinic of Endocrinology, Medical University-Sofia, 1431 Sofia, Bulgaria

Received 9 May 2011; Revised 3 July 2011; Accepted 24 July 2011

Academic Editor: Kazuya Yamagata

Copyright © 2012 Mei-Fang Zhong 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

We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK) and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF) with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS) and inducible/constitutive heme oxygenase (HO-1/HO-2) in GK. The endothelium-dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarity in vitro enhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK.