谷氨酰胺对2型糖尿病大鼠血糖和胰岛素抵抗的影响

Effect of glutamine on blood glucose and insulin resistance in type 2 diabetes rats

目的观察L-备氨酰胺对2型糖尿病大鼠血糖变化和胰岛素抵抗的影响并探讨可能机制。方法SD雄性大鼠47只，按随机数字表法分为4组：空白对照组（C组）10只、谷氨酰胺（glutamine，Gln）组（Gln组）10只、2型糖尿病组（DM组）12只、2型糖尿病俗氨酰胺组（DM＋Gln组）15只。实验动物分组饲养，2型糖尿病大鼠模型制作成功并稳定后予以Gin（1g·kg-1·d-1）继续灌胃3周，分别检测各组大鼠第1、6、9周末空腹血糖（fasting blood glucose，FBG）值和空腹血胰岛素（fasting insulin，FNS）值并计算胰岛素抵抗值（horncostasis model assessment-insulin resistance index，HOMA-IR）。于第9周末取大鼠腓肠肌检测肌细胞葡萄糖转移蛋白4（glucose transporter type4，GLUT4）向细胞膜转位量和细胞内葡萄糖转移蛋白4信使RNA（GLUT4mRNA）表达量。结果在第6周末，DM组和DM＋Gln组大鼠FBG分别升高为（16．3±3．7）mmol／L和（15．9±4．8）mmol]L，分别与c组（5．9±1．4）mmo]／L和Gln组（5．9±0．9）mmol／L相比差异有统计学意义（P〈0．05）。同时间点DM组和DM＋Gln组HOMA4R分别升高为（4．1±0．5）和（4．0±0．6），分别与C组（3．4±0．3）和Gln组（3．3±0．4）相比差异有统计学意义（P〈0．05）；在第9周末，DM＋Gln组FBG（15±9）mmol／L明显低于DM组（24±12）mmol／L（P〈0．05），DM＋Gln组HOMA-IR（3．0±0．6）明显低于DM组（3．7±0．4）（P〈0．05），同时间点c组（3．3±0．4）和Gln组（3．2±0.5）也明显低于DM组（P〈0．05）；4组之间GLUT4蛋白膜转位量和GLUT4mRNA差异无统计学意义（P〉0．05）；结论对2型糖尿病大鼠连续投入Gin3周可以增强胰岛素敏感性，维持血糖相对稳定，但其机制与葡萄糖转运体基因表达和蛋白转运无关。

Objective To observe the effect of glutamine （Gln） on blood glucose and insulin resistance in type 2 diabetes rats and to explore the possible mechanism. Methods Forty-seven healthy SD male rats were randomly divided into 4 groups： Control group（n=10）, Gln group（n=10）, Type 2 Diabetes group（n=12） and Gln and Type 2 Diabetes group（n=15）. After set up of the Type 2 Diabetes rat models successfully, Gin （1 g·kg-1·d-1） was administered orally by gavage for three weeks continuously. fasting blood glucose （FBG） and fasting insulin （FNS） were measured at the end of Week 1st, 6th and 9th, respectively. Then homeostasis model assessment-insulin resistance index （HOMA-IR） was calculated based on FBG and FNS. At the end of week 9th, mRNA and protein expression of glucose transporter type 4 （GLUT4） were measured by reverse transcriptive polymerase chain reaction （RT-PCR） and WB, respectively. Results At the end of the sixth week, FBG was significantly increased to （16.7±3.5） mmol/L and （15.9±4.8） mmol/L in DM and DM＋Gln groups, and there is no difference between these two groups. However, compared with C group （5.9±1.4） mmol/L and Gin group （5.9±0.9） mmol/L, FBG was highly raised in DM and DM＋Gln groups （P〈0.05）. Meanwhile, FNS was significantly increased to （4.1±0.5）and （4.0±0.6） in DM and DM＋G]n groups, compared with C group （34±0.3） and Gin group （3.3±0.4）, FBG was highly raised in DM and DM＋Gln groups（P〈0.05）. At the end of 9th week, FBG in DM group （24.5±11.8） mmol/L was significantly higher than that in DM＋Gln （15.2±9.6） mmol/L, HOMA-IR in DM group （3.7±0.4）was significantly higher than that in DM ＋Gin group （3.0±0.6） （P〈0.05）, Meanwhile, HOMA -IR in C group （3.3 ±0.4）and Gin group （3.2±0.5）were significantly lower than that in DM group（P〈0.05 ）. There were no significant different in mRNA and protein of GLUT4 among four groups （P〉0.05）. Conclusion Continually oral of Gin can stabilize the blood glucose and enhance insulin sensitivity of type 2 diabetes rats, which is able to help control blood glucose levels. But this activity is not associated with mRNA and protein translocation of GLUT4.