INSULIN AND ADIPOSE CONVERSION

长期目标是：1)了解分子机制 控制脂肪细胞特异性基因的表达 分化前脂肪细胞和成熟脂肪细胞；2)分化为 明确胰岛素在脂肪细胞基因激活和表达中的作用 压抑。我们计划继续我们对监管的研究 在分化和成熟过程中运行的机制 小鼠3T3-L1前脂肪细胞的体外培养。在这个模型系统中 分化伴随着大量的激活 与脂肪细胞特异性基因的发育增加有关 对胰岛素的反应性。在终末分化的细胞中 某些脂肪细胞特异性基因的表达是相互作用的 受胰岛素调节，与荷尔蒙在 激活脂肪生成和抑制脂肪分解。我们 克隆并部分鉴定了两个脂肪细胞基因( 422和122基因)，这两个基因都是转录激活的 在3T3-L1前脂肪细胞分化为“脂肪细胞”的过程中， 在成熟期也受到胰岛素的相互调节 脂肪细胞。3T3-L1的大量背景信息 细胞系统已经得到了关于生物化学的研究 脂肪分化计划和胰岛素的作用。 具体目标将是：1)确定基因 422和122基因的组织和结构 代表了两类具有储能和动员功能的基因 功能分别是2)识别和测序基因 控制422和122基因转录的元件 在前脂肪细胞分化和胰岛素刺激过程中，3)至 识别和表征相互作用的调节蛋白 422和122基因的控制元件，并确定 这种相互作用会改变转录，以及4)(以确定 胰岛素起增减作用的部位(S) 422和122 mRNAs的细胞水平，即 无论是通过改变基因转录还是通过改变 特定的信使核糖核酸周转率。这一现象的分子机制 将对实施监管的情况进行调查。

The LONG-TERM GOALS are: 1) to understand the molecular mechanisms that control the expression of adipocyte-specific genes both in differentiating preadipocytes and in mature adipocytes and 2) to define the role of insulin in adipocyte gene activation and repression. We plan to continue our studies on the regulatory mechanisms that operate during the differentiation and maturation of murine 3T3-L1 preadipocytes in culture. In this model system differentiation is accompanied by the activation of a large number of adipocyte-specific genes and the development of increased responsiveness to insulin. In the terminally differentiated cell the expression of certain adipocyte-specific genes is reciprocally regulated by insulin, consistent with the role of the hormone in the activation of lipogenesis and the inhibition of lipolysis. We have cloned and partially characterized two adipocyte genes (the 422 and 122 genes), both of which are transcriptionally activated during differentiation of 3T3-L1 preadipocytes into "adipocytes," and are also reciprocally regulated by insulin in the mature adipocyte. Considerable background information with the 3T3-L1 cell system has already been obtained on the biochemistry of the adipose differentiation program and on insulin action. The SPECIFIC AIMS will be: 1) to determine the genetic organization and structures of the 422 and 122 genes which represent two classes of genes having energy storage and mobilizing functions, respectively, 2) to identify and sequence the genetic elements which control transcription of the 422 and 122 genes during preadipocyte differentiation and insulin stimulation, 3) to identify and characterize the regulatory proteins that interact with control elements of the 422 and 122 genes and to establish how this interaction alters transcription, and 4) (to determine the site(s) at which insulin acts to increase and decrease, respectively, the cellular levels of the 422 and 122 mRNAs, i.e. whether by altering gene transcription or by altering the rate of specific mRNA turnover. The molecular mechanisms by which this regulation is exerted will be investigated.