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，和2） 确定胰岛素在脂肪细胞基因激活中的作用， 镇压 我们计划继续研究规管 在分化和成熟过程中起作用的机制 的小鼠3 T3-L1前脂肪细胞的培养。 在该模型系统中 分化伴随着大量的 脂肪细胞特异性基因和增加的发展 对胰岛素的反应。 在终末分化的细胞中 某些脂肪细胞特异性基因的表达被抑制， 由胰岛素调节，与激素在 脂肪生成的激活和脂肪分解的抑制。 我们 克隆并部分表征了两个脂肪细胞基因（ 422和122个基因），两者都是转录激活的 在3 T3-L1前脂肪细胞分化为“脂肪细胞”的过程中， 在成熟的哺乳动物中， 脂肪细胞 关于3 T3-L1的大量背景信息 细胞系统已经获得了生物化学的 脂肪分化程序和胰岛素作用。 具体目标是：1）确定遗传 422和122基因的组织和结构， 代表了两类具有能量储存和动员功能的基因 功能，分别，2）识别和序列的遗传 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期间，3） 识别和表征相互作用的调节蛋白 与422和122基因的控制元件，并建立如何 这种相互作用改变转录，和4）（以确定 胰岛素作用于增加和减少的部位， 422和122 mRNA的细胞水平，即， 无论是通过改变基因转录还是通过改变 特异性mRNA周转。 这一过程的分子机制 监管将被调查。

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.