STIMULATION OF GLUCOSE-TRANSPORT BY INSULIN AND NOREPINEPHRINE IN ISOLATED RAT BROWN ADIPOCYTES
STIMULATION OF GLUCOSE-TRANSPORT BY INSULIN AND NOREPINEPHRINE IN ISOLATED RAT BROWN ADIPOCYTES
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DOI：
10.1152/ajpcell.1989.257.4.c714
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发表时间：
1989-10-01
影响因子：
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通讯作者：
BUKOWIECKI, LJ
中科院分区：
文献类型：
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作者：
MARETTE, A;BUKOWIECKI, LJ
研究了胰岛素和去甲肾上腺素对离体大鼠棕色脂肪细胞葡萄糖转运、葡萄糖摄取和细胞呼吸的影响。分别使用[U-14 C]-D-葡萄糖和2-脱氧-[1，2 - 3 H]-D-葡萄糖测定葡萄糖转运和摄取。棕色脂肪细胞呼吸测定极谱法。剂量反应实验表明，在10-11和10-7 M之间，胰岛素刺激D-葡萄糖转运和2-脱氧葡萄糖摄取，最大刺激为4至6倍。在没有胰岛素的情况下，去甲肾上腺素浓度范围从10-10至10-7 M也增强葡萄糖转运和摄取，最大刺激2至4倍。用α-和β-肾上腺素能激动剂和拮抗剂的研究表明，去甲肾上腺素的作用主要通过β-肾上腺素能通路二丁酰环AMP和3-异丁基-1-甲基黄嘌呤也增加葡萄糖转运，表明去甲肾上腺素的作用是环AMP依赖性的。此外，去甲肾上腺素（10-8 M）增强胰岛素对葡萄糖转运的敏感性[半最大速度常数（1/2 Vmax）]，但未能增强胰岛素反应性（Vmax）。另一方面，胰岛素（10-9 M）对基础呼吸无影响，但可快速抑制去甲肾上腺素（10-7 M）的产热效应，抑制率> 50%。这些结果证明（1）在不存在胰岛素的情况下，生理浓度的去甲肾上腺素刺激葡萄糖经由α-葡萄糖转运。肾上腺素能途径，（2）神经激素协同增强棕色脂肪细胞对葡萄糖转运的次最大胰岛素反应，和（3）胰岛素抵消去甲肾上腺素对棕色脂肪细胞产热的影响，尽管这两种激素都增强葡萄糖摄取。
The effects of insulin and norepinephrine on glucose transport, glucose uptake, and cell respiration were investigated in isolated rat brown adipocytes. Glucose transport and uptake were determined using [U-14C]-D-glucose and 2-Deoxy-[1,2-3H]-D-glucose, respectively. Brown adipocyte respiration was measured polarographically. Dose-response experiments revealed that insulin stimulated D-glucose transport and 2-deoxyglucose uptake between 10-11 and 10-7 M with a maximal four- to sixfold stimulation. In the absence of insulin, norepinephrine concentrations ranging from 10-10 to 10-7 M also enhanced glucose transport and uptake with a maximal two- to fourfold stimulation. Experiments with .alpha.- and .beta.-adrenergic agonists and antagonists showed that the effect of norepinephrine was predominantly mediated via .beta.-adrenergic pathways. Dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine also increased glucose transport, suggesting that the effects of norepinephrine are cyclic AMP dependent. Moreover, norepinephrine (10-8 M) enhanced insulin sensitivity for glucose transport [half-maximum velocity constant (1/2 Vmax)] but failed to potentiate insulin responsiveness (Vmax). On the other hand, insulin (10-9 M) had no effect on basal respiration but rapidly inhibited the calorigenic effect of norepinephrine (10-7 M) by > 50%. These results demonstrate that (1) in the absence of insulin, physiological concentrations of norepinephrine stimulate glucose transport via .alpha.-adrenergic pathways, (2) the neurohormone synergistically potentiates brown adipocyte submaximal insulin responses for glucose transport, and (3) insulin counteracts the effects of norepinephrine on brown adipocyte thermogenesis despite the fact that both hormones enhance glucose uptake.