Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin
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- Mei-Fang Zhong
- Department 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
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- Wei-Li Shen
- Department 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
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- Masaki Tabuchi
- Department of Pharmacology, Kinki University School of Medicine, Osaka 589-8511, Japan
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- Kyoko Nakamura
- Department of Pharmacology, Kinki University School of Medicine, Osaka 589-8511, Japan
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- Yi-Chen Chen
- Department 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
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- Cong-Zhen Qiao
- Department 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
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- Jin He
- Department 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
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- Jie Yang
- Department 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
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- Chuan Zhang
- Division of New Drug Research, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
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- Zdravko Kamenov
- Clinic of Endocrinology, Medical University-Sofia, 1431 Sofia, Bulgaria
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- Hideaki Higashino
- Department of Pharmacology, Kinki University School of Medicine, Osaka 589-8511, Japan
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- Hong Chen
- Department 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
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説明
<jats:p>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<jats:italic>in vitro</jats:italic>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.</jats:p>
収録刊行物
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- Experimental Diabetes Research
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Experimental Diabetes Research 2012 1-16, 2012
Wiley
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キーワード
- Blood Glucose
- Male
- Nitric Oxide Synthase Type III
- Rats, Inbred OLETF
- Vasodilator Agents
- Nitric Oxide Synthase Type II
- Animals
- Hypoglycemic Agents
- Insulin
- Enzyme Inhibitors
- Rats, Wistar
- Aorta
- Dose-Response Relationship, Drug
- Age Factors
- Rats
- Vasodilation
- Disease Models, Animal
- Carotid Arteries
- Diabetes Mellitus, Type 2
- Heme Oxygenase (Decyclizing)
- Endothelium, Vascular
- Diabetic Angiopathies
- Research Article
詳細情報 詳細情報について
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- CRID
- 1360567186294720768
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- ISSN
- 16875303
- 16875214
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- PubMed
- 21977022
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE