ROLE OF INSULIN IN GROWTH HORMONE-STIMULATED 3T3-CELL ADIPOGENESIS

ROLE OF INSULIN IN GROWTH HORMONE-STIMULATED 3T3-CELL ADIPOGENESIS
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DOI:
10.1210/endo-122-5-2084
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发表时间:
1988-05-01
期刊:
影响因子:
4.8
通讯作者:
SONENBERG, M
SONENBERG, M
中科院分区:
医学2区
文献类型:
--
作者:
GULLER, S;CORIN, RE;SONENBERG, M

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研究了胰岛素在GH刺激的3 T3-F442 A成纤维细胞脂肪形成过程中的作用。脂肪形成是限定培养基(DM),如通过甘油-3-磷酸脱氢酶活性水平量化的,揭示了脂肪形成过程中存在对胰岛素和GH的严格要求。诱导半数最大脂肪形成所需的胰岛素浓度约为20 nM。胰岛素样生长因子I在促进脂肪形成方面不如胰岛素有效,表明分化过程中胰岛素的作用最有可能是通过胰岛素受体介导的。细胞活力不受胰岛素缺乏的影响,通过集落形成效率或台盼蓝排除法判断。从补充有1 nM重组人GH的DM中删除胰岛素将甘油-3-磷酸脱氢酶活性降低至未诱导水平。去除其他个别DM constituents没有这种效果。生长因子成纤维细胞生长因子,血小板衍生生长因子,蛙皮素没有替代胰岛素在GH刺激的脂肪形成。在基于血清的分化过程中观察到的细胞数量特征性增加,反映了年轻脂肪细胞的克隆扩增,在补充胰岛素和GH的DM中没有发生,这表明GH、胰岛素和胰岛素样生长因子I以外的血清因子对该事件是必要的。这些结果表明,胰岛素的功能与GH作为分化信号的共诱导剂。
The role of insulin during GH-stimulated adipogenesis of 3T3-F442A fibroblasts was investigated. Adipogenesis is defined medium (DM), as quantified by the level of glycerol-3-phosphate dehydrogenase activity, revealed that there existed a strict requirement for both insulin and GH during adipogenesis. The concentration of insulin required to elicit half-maximal adipogenesis was approximately 20 nM. Insulin-like growth factor I was less effective than insulin in promoting adipogenesis, indicating that insulin action during differentiation was most likely mediated through the insulin receptor. Cellular viability was not compromised by the absence of insulin, as judged by colony-forming efficiency or trypan blue exclusion. Deletion of insulin from DM supplemented with 1 nM recombinant human GH reduced glycerol-3-phosphate dehydrogenase activity to uninduced levels. Removal of other individual DM constitutents did not have this effect. The growth factors fibroblast growth factor, platelet-derived growth factor, and bombesin did not substitute for insulin during GH-stimulated adipogenesis. The characteristic increase in cell number observed during serum-based differentiation, reflecting clonal expansion of young adipocytes, did not occur in DM supplemented with insulin and GH, suggesting that serum factors other than GH, insulin, and insulin-like growth factor I were necessary for this event. These results suggest that insulin functions in concert with GH as a coinducer of the differentiating signals.