Fasshauer Mathias, Klein Johannes, Lossner Ulrike, Paschke Ralf
Department of Internal Medicine III, University of Leipzig, Leipzig 04103, Germany.
Eur J Endocrinol. 2002 Oct;147(4):553-9. doi: 10.1530/eje.0.1470553.
Galectin-12 has recently been shown to be a predominantly adipocyte-expressed protein which is stimulated by insulin-sensitizing thiazolidinediones and possesses apoptosis-inducing activity.
To further clarify galectin-12 regulation and its potential involvement in the development of insulin resistance, 3T3-L1 adipocytes were chronically treated with various hormones known to impair insulin sensitivity, and galectin-12 mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction.
Treatment of 3T3-L1 cells for 16 h with 10 micromol/l isoproterenol, 100 nmol/l insulin, 0.6 nmol/l tumor necrosis factor alpha (TNFalpha), and 100 nmol/l dexamethasone reduced galectin-12 gene expression between 47% and 85%. These negative effects were dose-dependent with significant inhibition detectable at concentrations as low as 10 nmol/l isoproterenol, 0.06 nmol/l TNFalpha, and 1 nmol/l dexamethasone. Furthermore, the inhibitory effect of isoproterenol could be almost completely reversed by pretreatment with the beta-adrenergic antagonist propranolol and mimicked by stimulation of G(S)-proteins with cholera toxin or by activation of adenylyl cyclase with forskolin and dibutyryl-cAMP.
Our results suggest that galectin-12 is an adipocyte-expressed protein which is downregulated by various insulin resistance-inducing hormones. These findings imply a role for galectin-12 in the pathogenesis of insulin resistance.
最近研究表明，半乳糖凝集素-12是一种主要在脂肪细胞中表达的蛋白质，可被胰岛素增敏剂噻唑烷二酮类药物激活，并具有诱导细胞凋亡的活性。
为了进一步阐明半乳糖凝集素-12的调控机制及其在胰岛素抵抗发生发展中的潜在作用，我们用已知会损害胰岛素敏感性的多种激素对3T3-L1脂肪细胞进行长期处理，并用实时定量逆转录聚合酶链反应检测半乳糖凝集素-12的信使核糖核酸。
用10微摩尔/升异丙肾上腺素、100纳摩尔/升胰岛素、0.6纳摩尔/升肿瘤坏死因子α（TNFα）和100纳摩尔/升地塞米松处理3T3-L1细胞16小时，可使半乳糖凝集素-12基因表达降低47%至85%。这些负面影响呈剂量依赖性，在低至10纳摩尔/升异丙肾上腺素、0.06纳摩尔/升TNFα和1纳摩尔/升地塞米松的浓度下即可检测到显著抑制作用。此外，用β-肾上腺素能拮抗剂普萘洛尔预处理可几乎完全逆转异丙肾上腺素的抑制作用，用霍乱毒素刺激G(S)蛋白或用福斯可林和二丁酰环磷腺苷激活腺苷酸环化酶也可模拟这种抑制作用。
我们的结果表明，半乳糖凝集素-12是一种在脂肪细胞中表达的蛋白质，可被多种诱导胰岛素抵抗的激素下调。这些发现提示半乳糖凝集素-12在胰岛素抵抗的发病机制中起作用。
