Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding protein 1 gene transcription by hormones and provision of amino acids in rat hepatocytes.
Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding protein 1 gene transcription by hormones and provision of amino acids in rat hepatocytes.
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DOI：
10.1210/mend.7.12.7511786
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发表时间：
1993-12
影响因子：
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通讯作者：
C. Pao;P. Farmer;Svijetlana Begovic;B. C. Villafuerte;Guang-Jer Wu;D. Robertson;L. Phillips
中科院分区：
文献类型：
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作者：
C. Pao;P. Farmer;Svijetlana Begovic;B. C. Villafuerte;Guang-Jer Wu;D. Robertson;L. Phillips
胰岛素样生长因子-I（IGF-I）和胰岛素样生长因子结合蛋白-1（IGFBP-1）的合成在糖尿病和营养不良中发生改变，但对其基本过程知之甚少。为了研究分子机制，我们研究了大鼠肝细胞原代培养物中IGF-I和IGFBP-1基因转录的调控。IGF-I和IGFBP-1基因的转录被测量为[α-32 P]UTP掺入分离的细胞核中的预起始信息。IGFBP-1基因转录对氨基酸浓度从5倍降低至0.5倍大鼠动脉血浆水平不敏感。然而，IGF-I基因转录下降60-70%，以响应减少提供的氨基酸。用10（-9）M胰岛素培养使IGFBP-1基因转录降低50%，低于对照水平（10-11 M），但不影响IGF-I基因转录; 10（-6）M胰岛素使IGF-I基因转录提高2倍。在胰岛素浓度急性降低后，IGFBP-1转录在30 min内开始升高，但IGF-I基因转录在120 min内无变化。同样，胰岛素刺激IGF-I基因转录需要3-6 h，但在加入10（-6）M胰岛素后15 min内可检测到IGFBP-1基因转录降低40%，胰岛素对IGFBP-1转录的抑制不受放线菌酮的影响。胰岛素对IGFBP-1基因转录的影响不被佛波酯所模拟或拮抗。（250字处删节）
Synthesis of insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) is altered in diabetes and malnutrition, but underlying processes are poorly understood. To study molecular mechanisms, we examined regulation of IGF-I and IGFBP-1 gene transcription in primary cultures of rat hepatocytes. Transcription of the IGF-I and IGFBP-1 genes was measured as incorporation of [alpha-32P]UTP into preinitiated message in isolated nuclei. IGFBP-1 gene transcription was not sensitive to reduction in amino acid concentration from 5x to 0.5x rat arterial plasma levels. However, IGF-I gene transcription fell 60-70% in response to reduced provision of amino acids. Culture with 10(-9) M insulin lowered IGFBP-1 gene transcription 50% below control levels (10-11 M) but did not affect IGF-I gene transcription; 10(-6) M insulin raised IGF-I gene transcription 2-fold. After an acute reduction in insulin concentration, IGFBP-1 transcription began to rise within 30 min, but IGF-I gene transcription was unchanged over 120 min. Similarly, 3-6 h were required for stimulation of IGF-I gene transcription by insulin, but a 40% decrease in IGFBP-1 gene transcription could be detected within 15 min after adding 10(-6) M insulin, and suppression of IGFBP-1 transcription by insulin was unaffected by the presence of cycloheximide. Effects of insulin on IGFBP-1 gene transcription were not mimicked or antagonized by phorbol ester.(ABSTRACT TRUNCATED AT 250 WORDS)