Insulin renders diabetic rats resistant to acute ischemic stroke by arresting nitric oxide reaction with superoxide to form peroxynitrite

Journal of Biomedical Science

Shiang-Suo Huang³  Yuan-Ji Day¹  Dai-Er Li⁴  Meng-Hsuan Yang⁴  Jiuan-Miaw Liao²  Jiung-Pang Huang⁴  Li-Man Hung⁴ 

[1] Department of Anesthesiology, Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan;Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung, Taiwan;Department of Pharmacology and Institute of Medicine, Chung Shan Medical University and Department of Pharmacy, Chung Shan Medical University Hospital, No.110, Sec. 1, Jianguo N. Rd, Taichung City 402, Taiwan;Department and Graduate Institute of Biomedical Sciences and Healthy Aging Research Center, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan

关键词: Peroxynitrite;    Superoxide;    Nitric oxide;    Insulin;    Ischemic stroke;    Diabetes;   

Others  :  1146328
DOI  :  10.1186/s12929-014-0092-0

 received in 2014-07-03, accepted in 2014-09-02,  发布年份 2014

【 摘 要 】

Background

The functions of free radicals on the effects of insulin that result in protection against cerebral ischemic insult in diabetes remain undefined. This present study aims to explain the contradiction among nitric oxide (NO)/superoxide/peroxynitrite of insulin in amelioration of focal cerebral ischemia¿reperfusion (FC I/R) injury in streptozotocin (STZ)-diabetic rats and to delineate the underlying mechanisms. Long-Evans male rats were divided into three groups (age-matched controls, diabetic, and diabetic treated with insulin) with or without being subjected to FC I/R injury.

Results

Hyperglycemia exacerbated microvascular functions, increased cerebral NO production, and aggravated FC I/R-induced cerebral infarction and neurological deficits. Parallel with hypoglycemic effects, insulin improved microvascular functions and attenuated FC I/R injury in STZ-diabetic rats. Diabetes decreased the efficacy of NO and superoxide production, but NO and superoxide easily formed peroxynitrite in diabetic rats after FC I/R injury. Insulin treatment significantly rescued the phenomenon.

Conclusions

These results suggest that insulin renders diabetic rats resistant to acute ischemic stroke by arresting NO reaction with superoxide to form peroxynitrite.

【 授权许可】

   
2014 Hung et al.; licensee BioMed Central Ltd.

【 图 表 】

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