Insulin but not IGF-I is required for the maintenance of the adipose phenotype in the adipogenic cell line 1246.
Insulin but not IGF-I is required for the maintenance of the adipose phenotype in the adipogenic cell line 1246.
复制标题
维持脂肪形成细胞系1246中的脂肪表型需要胰岛素，而不是IGF-I。
DOI：
10.1007/s11626-999-0104-7
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Lepak,N
中科院分区：
文献类型：
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作者：
Serrero,G;Lepak,N
采用小鼠1246型同时具有胰岛素和胰岛素样生长因子I （IGF-I）受体的成脂细胞系，研究了IGF-I和胰岛素对脂肪细胞前体增殖和向成熟脂肪细胞分化的作用。结果表明，胰岛素和igf - 1均能刺激1246脂肪细胞前体的增殖，其中igf - 1的作用强于胰岛素。剂量反应研究表明，这两种多肽在与自身受体结合的生理浓度下起作用。相比之下，胰岛素和IGF-I刺激终端脂肪分化的能力的比较表明，只有胰岛素在生理浓度下添加时才有活性。igf - 1不能刺激脂肪细胞分化，除非在超生理浓度（100 ng/ml及以上）允许其与1246个细胞上的胰岛素受体结合。对脂肪分化早期和晚期标志物表达的时序研究表明，即使在没有胰岛素的情况下，脂肪分化相关蛋白（ADRP）、脂蛋白脂肪酶（LPL）和脂肪酸结合蛋白（FAB）等标志物的诱导也会发生。然而，当细胞在没有胰岛素的情况下维持分化后，早期和晚期分化标志物的水平下降到低于未分化细胞的水平。这些数据表明，尽管胰岛素对于脂肪分化程序的早期启动不是必需的，但它对于脂肪细胞表型的维持是严格需要的，并且不能被igf - 1所取代。
The mouse adipogenic cell line 1246 which possesses both insulin and insulin-like growth factor I (IGF-I) receptors was used to investigate the role of IGF-I and insulin on the proliferation of adipocyte precursors and their differentiation into mature adipocytes. Results indicate that both insulin and IGF-I stimulate the proliferation of the 1246 adipocyte precursors with IGF-I being slightly more potent than insulin. Dose-response studies indicated that both polypeptides acted at physiological concentrations corresponding to binding to their own receptors. In contrast, comparison of insulin and IGF-I capacity to stimulate terminal adipose differentiation indicated that only insulin was active when added at physiological concentrations. IGF-I could not stimulate adipocyte differentiation except at supraphysiological concentrations (100 ng/ml and above) permitting its binding to the insulin receptors on 1246 cells. Time course study of expression of early and late markers of adipose differentiation indicated that the induction of markers such as adipose differentiation-related protein (ADRP), lipoprotein lipase (LPL) and fatty acid binding protein (FAB) took place even in the absence of insulin. However, the level of early and late differentiation markers decreased to a level below the one found in undifferentiated cells when cells had been maintained in the absence of insulin after differentiation had been initiated. These data indicate that although insulin is not necessary for the early onset of the adipose differentiation program, it is stringently required for the maintenance of the adipocyte phenotype and cannot be substituted by IGF-I.