Dexamethasone treatment causes resistance to insulin-stimulated cellular potassium uptake in the rat.
Dexamethasone treatment causes resistance to insulin-stimulated cellular potassium uptake in the rat.
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地塞米松治疗会导致大鼠对胰岛素刺激的细胞钾摄取产生抵抗。
DOI：
10.1152/ajpcell.00111.2004
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
McDonough,AliciaA
中科院分区：
文献类型：
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作者：
Rhee,MichaelS;Perianayagam,Anjana;Chen,Pei;Youn,JangH;McDonough,AliciaA
接受糖皮质激素治疗的患者骨骼肌哇巴因结合部位升高。在人工合成的糖皮质激素地塞米松治疗14天后，肌肉中发现的主要Na+-K+-ATPase亚型蛋白α2和β1增加了50%。这项研究探讨了地塞米松诱导的肌肉NKA池增加是否导致胰岛素刺激的细胞K+摄取增加，从而导致低钾血症。分别以0.02 mg·kg-1·d-1·d-1地塞米松和0.1 mg·kg-1·d-1的−-1·d-−-1给药，共14天(低地塞米松，n=5对)或0.1 mg·kg-1-−-1-d-−-1(高地塞米松，n=6对)。清醒大鼠以5mU·kg-1·−-1·−-1的速度输注胰岛素2.5h以上。通过测量胰岛素输注过程中维持血浆K+和葡萄糖浓度恒定所需的外源性K+输注速率(\Batchmode\Documentclass[fleqn，10pt，LegalPaper]{文章}\usepackage{amssymb}\usepackage{amsfonts}\usepackage{amsath}\PageStyle{Empty}\Begin{Document}\(\mathit{K}{\mathit{inf}}^{{+}}\)和葡萄糖输注速率(Ginf))来评估胰岛素刺激的细胞内K+和葡萄糖摄取率。正如先前报道的那样，两种剂量的地塞米松都能减少胰岛素刺激的葡萄糖摄取。−1·h−1中GINF为10.2±0.6，低剂量组为5.8±0.8，高剂量组为5.2±0.6。高DEX处理也减少了胰岛素刺激的K+摄取。BATCHMODE\DocumentClass[fleqn，10pt，LegalPaper]{文章}\usepackage{amssymb}\usepackage{amsFonts}\usepackage{amsath}\PageStyle{Empty}\Begin{Document}\(Mathit{K}_{\mathit{inf}}^{{+}}\)\end{Document}(单位：−1·h−1)：安慰剂组为0.5 3±0.0 8，低剂量组为0.49±0.14，高剂量组为0.2 7±0.0 8。地塞米松治疗不改变尿K+排泄量。免疫印迹法检测低地塞米松组大鼠NKAα2亚型水平无明显变化，高地塞米松组大鼠比目鱼肌和腓肠肌NKA NKA 2亚型水平分别升高38±15%和67±3%。NKAα1-亚型水平无明显变化。这些结果为慢性地塞米松治疗过程中K+清除的胰岛素抵抗提供了新的证据。尽管肌肉钠泵池大小增加，但胰岛素刺激的细胞K+摄取显著降低。
Patients treated with glucocorticoids have elevated skeletal muscle ouabain binding sites. The major Na+-K+-ATPase (NKA) isoform proteins found in muscle, α2and β1, are increased by 50% in rats treated for 14 days with the synthetic glucocorticoid dexamethasone (DEX). This study addressed whether the DEX-induced increase in the muscle NKA pool leads to increased insulin-stimulated cellular K+uptake that could precipitate hypokalemia. Rats were treated with DEX or vehicle via osmotic minipumps at one of two doses: 0.02 mg·kg−1·day−1for 14 days (low DEX;n= 5 pairs) or 0.1 mg·kg−1·day−1for 7 days (high DEX;n= 6 pairs). Insulin was infused at a rate of 5 mU·kg−1·min−1over 2.5 h in conscious rats. Insulin-stimulated cellular K+and glucose uptake rates were assessed in vivo by measuring the exogenous K+infusion (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathit{K}_{\mathit{inf}}^{{+}}\) \end{document}) and glucose infusion (Ginf) rates needed to maintain constant plasma K+and glucose concentrations during insulin infusion. DEX at both doses decreased insulin-stimulated glucose uptake as previously reported. Ginf(in mmol·kg−1·h−1) was 10.2 ± 0.6 in vehicle-treated rats, 5.8 ± 0.8 in low-DEX-treated rats, and 5.2 ± 0.6 in high-DEX-treated rats. High DEX treatment also reduced insulin-stimulated K+uptake. \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathit{K}_{\mathit{inf}}^{{+}}\) \end{document}(in mmol·kg−1·h−1) was 0.53 ± 0.08 in vehicle-treated rats, 0.49 ± 0.14 in low-DEX-treated rats, and 0.27 ± 0.08 in high-DEX-treated rats. DEX treatment did not alter urinary K+excretion. NKA α2-isoform levels in the low-DEX-treated group, measured by immunoblotting, were unchanged, but they increased by 38 ± 15% (soleus) and by 67 ± 3% (gastrocnemius) in the high-DEX treatment group. The NKA α1-isoform level was unchanged. These results provide novel evidence for the insulin resistance of K+clearance during chronic DEX treatment. Insulin-stimulated cellular K+uptake was significantly depressed despite increased muscle sodium pump pool size.