α1- and β1-adrenoceptor signaling fully compensates for β3-adrenoceptor deficiency in brown adipocyte norepinephrine-stimulated glucose uptake
α1- and β1-adrenoceptor signaling fully compensates for β3-adrenoceptor deficiency in brown adipocyte norepinephrine-stimulated glucose uptake
复制标题
DOI：
10.1210/en.2004-1104
复制
发表时间：
2005-05-01
期刊：
影响因子：
4.8
通讯作者：
Bengtsson, T
中科院分区：
文献类型：
--
作者：
Chernogubova, E;Hutchinson, DS;Bengtsson, T
为了评估除β(3)-肾上腺素能受体以外的肾上腺素能受体亚型在褐色脂肪细胞去甲肾上腺素介导的葡萄糖摄取中的相对作用和潜在贡献，我们在这里分析了野生型和β(3)-肾上腺素能受体敲除（KO）小鼠棕色脂肪细胞原代培养中肾上腺素能激活的葡萄糖摄取。在对照细胞中，除了高水平的β(3)-肾上腺素能受体mRNA外，α (1A)-、α (1D)-和β(1)-肾上腺素能受体mRNA水平相对较低，其他肾上腺素能受体未见明显表达。β (3)- ko棕色脂肪细胞中α (1A)-、α (1D)-和β(1)-肾上腺素能受体mRNA水平未发生变化，表明β(3)-肾上腺素能受体消融不影响培养棕色脂肪细胞中肾上腺素能基因的表达。正如预期的那样，β(3)-肾上腺素能受体激动剂BRL-37344和CL-316 243不会诱导β (3)-KO棕色脂肪细胞摄取2-脱氧-d -葡萄糖。令人惊讶的是，内源性肾上腺素能神经递质去甲肾上腺素在野生型和β (3)-KO棕色脂肪细胞中诱导了相同的浓度依赖性2-脱氧-d -葡萄糖摄取。本研究表明β(1)-肾上腺素能受体，以及在较小程度上β(1)-肾上腺素能受体，在功能上弥补了葡萄糖摄取中β(3)-肾上腺素能受体的缺失。β(1)-肾上腺素能受体通过cAMP/蛋白激酶a /磷脂酰肌醇3激酶途径激活葡萄糖摄取，刺激传统和新型蛋白激酶Cs。α(1)-肾上腺素能受体成分（在野生型细胞中不明显）在β (3)-KO细胞中通过磷脂酰肌醇3-激酶和蛋白激酶C途径刺激葡萄糖摄取。
To assess the relative roles and potential contribution of adrenergic receptor subtypes other than the beta(3)-adrenergic receptor in norepinephrine-mediated glucose uptake in brown adipocytes, we have here analyzed adrenergic activation of glucose uptake in primary cultures of brown adipocytes from wild-type and beta(3)-adrenergic receptor knockout (KO) mice. In control cells in addition to high levels of beta(3)-adrenergic receptor mRNA, there were relatively low alpha(1A)-, alpha(1D)-, and moderate beta(1)-adrenergic receptor mRNA levels with no apparent expression of other adrenergic receptors. The levels of alpha(1A)-, alpha(1D)-, and beta(1)-adrenergic receptor mRNA were not changed in the beta(3)-KO brown adipocytes, indicating that the beta(3)-adrenergic receptor ablation does not influence adrenergic gene expression in brown adipocytes in culture. As expected, the beta(3)-adrenergic receptor agonists BRL-37344 and CL-316 243 did not induce 2-deoxy-D-glucose uptake in beta(3)-KO brown adipocytes. Surprisingly, the endogenous adrenergic neurotransmitter norepinephrine induced the same concentration-dependent 2-deoxy-D-glucose uptake in wild-type and beta(3)-KO brown adipocytes. This study demonstrates that beta(1)-adrenergic receptors, and to a smaller degree beta(1)-adrenergic receptors, functionally compensate for the lack of beta(3)-adrenergic receptors in glucose uptake. beta(1)-Adrenergic receptors activate glucose uptake through a cAMP/protein kinase A/phosphatidylinositol 3-kinase pathway, stimulating conventional and novel protein kinase Cs. The alpha(1)-adrenergic receptor component ( that is not evident in wild-type cells) stimulates glucose uptake through a phosphatidylinositol 3-kinase and protein kinase C pathway in the beta(3)-KO cells.