Effects of dexamethasone in vivo and in vitro on hexose transport in brain microvasculature

Effects of dexamethasone in vivo and in vitro on hexose transport in brain microvasculature
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DOI:
10.1023/a:1022434721114
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发表时间:
1998-05-01
影响因子:
4.4
通讯作者:
McCall, AL
McCall, AL
中科院分区:
医学3区
文献类型:
--
作者:
Chipkin, SR;van Bueren, A;McCall, AL

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糖皮质激素可诱导高胰岛素血症、高血糖症,并抑制主动脉内皮对葡萄糖的转运。高剂量糖皮质激素用于许多疾病,但对脑葡萄糖转运或代谢的影响尚不清楚。本研究验证了糖皮质激素影响脑微血管内皮细胞葡萄糖转运或代谢的假设。雄性大鼠接受地塞米松(DEX)皮下注射蔗糖喂养长达7天。与对照组相比,DEX/蔗糖处理大鼠的脑微血管显示GLUT 1和脑葡萄糖提取增加。体内葡萄糖转运与高胰岛素血症相关。用低剂量链脲佐菌素预处理可减弱高胰岛素血症,并防止DEX诱导的葡萄糖提取增加。相反,在体外暴露于DEX的分离的脑微血管显示2-脱氧葡萄糖摄取和葡萄糖氧化的抑制。我们得出结论,DEX/蔗糖治疗在体内增加血脑葡萄糖转运的方式,需要慢性高胰岛素血症的影响。这些作用超越了高血糖症或DEX的任何直接抑制作用。
Glucocorticoids induce hyperinsulinemia, hyperglycemia, and depress glucose transport by aortic endothelium. High glucocorticoid doses are used for many diseases, but with unknown effects on brain glucose transport or metabolism. This study tested the hypothesis that glucocorticoids affect glucose transport or metabolism by brain microvascular endothelium. Male rats received dexamethasone (DEX) sc with sucrose feeding for up to seven days. Cerebral microvessels from rats treated with DEX/sucrose demonstrated increased GLUT1 and brain glucose extraction compared to controls. Glucose transport in vivo correlated with hyperinsulinemia. Pre-treatment with low doses of streptozotocin blunted hyperinsulinemia and prevented increased glucose extraction induced by DEX. in contrast, isolated brain microvessels exposed to DEX in vitro demonstrated suppression of 2-deoxyglucose uptake and glucose oxidation. We conclude that DEX/sucrose treatment in vivo increases blood-brain glucose transport in a manner that requires the effects of chronic hyperinsulinemia. These effects override any direct inhibitory effects of either hyperglycemia or DEX.