Glutamate permeability at the blood-brain barrier in insulinopenic and insulin-resistant rats.

Glutamate permeability at the blood-brain barrier in insulinopenic and insulin-resistant rats.
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DOI:
10.1016/j.metabol.2009.07.022
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发表时间:
2010-02
影响因子:
9.8
通讯作者:
Fernstrom, John D.
Fernstrom, John D.
中科院分区:
医学1区
文献类型:
--
作者:
Hawkins, Richard A.;Mokashi, Ashwini;DeJoseph, Mary R.;Vina, Juan R.;Fernstrom, John D.

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用胰岛素缺乏(链脲佐菌素(STZ))和胰岛素抵抗(饮食诱导肥胖(DIO))的糖尿病大鼠模型,研究糖尿病对脑谷氨酸(GLU)摄取的影响。在STZ研究中,成年雄性SD大鼠静脉注射STZ(65 mg/kg)或赋形剂,3周后进行研究。STZ大鼠血浆葡萄糖、酮体和支链氨基酸水平升高;在正常和血浆GLU浓度显著升高的情况下,STZ和对照组大鼠脑对GLU的摄取都非常低。在DIO研究中,大鼠摄入美味的高能量饮食2周,然后被分成体重等级:最重的三分位数的大鼠被指定为DIO,最轻的三分位数饮食抵抗(DR)的大鼠,以及中等三分位数对照组的大鼠。DIO和DR大鼠继续高能量饮食4周以上,而对照组大鼠则切换到标准大鼠饮食。所有大鼠在6周时进行研究(在血浆GLU浓度正常或升高的情况下进行亚组检查)。Dio大鼠比DR或对照组大鼠进食更多,体重更重,血浆瘦素水平和胰岛素/血糖比率更高。在所有饮食组中,血脑屏障显示非常低的GLU穿透率,并且不受血浆GLU浓度的影响。大脑对GLU的摄取在不同饮食组之间也没有差异。综上所述,结果表明,在所研究的条件下,两种糖尿病模型的血脑屏障对GLU的穿透保持完好。
The influence of diabetes on brain glutamate (GLU) uptake was studied in insulinopenic (streptozotocin (STZ)) and insulin-resistant (diet-induced obesity (DIO)) rat models of diabetes. In the STZ study, adult male Sprague-Dawley rats were treated with STZ (65 mg/kg iv) or vehicle and studied 3 weeks later. STZ rats had elevated plasma levels of glucose, ketone bodies and branched-chain amino acids; brain uptake of GLU was very low in both STZ and control rats, examined under conditions of normal and greatly elevated (by iv infusion) plasma GLU concentrations. In the DIO study, rats ingested a palatable, high-energy diet for 2 weeks, and were then divided into weight tertiles: rats in the heaviest tertile were designated DIO, rats in lightest tertile diet-resistant (DR), and rats in the intermediate tertile controls. DIO and DR rats continued to consume the high-energy diet for 4 more weeks, while control rats were switched to standard rat chow. All rats were studied at 6 weeks (subgroups were examined under conditions of normal or elevated plasma GLU concentrations). DIO rats ate more food and were heavier than DR or control rats, and had higher plasma leptin levels and insulin:glucose ratios. In all diet groups, the BBB showed very low GLU penetration, and was unaffected by plasma GLU concentration. Brain GLU uptake also did not differ among the diet groups. Together, the results indicate that the BBB remains intact to the penetration of GLU in two models of diabetes under the conditions examined.
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