Alexander-Bridges M, Buggs C, Giere L, Denaro M, Kahn B, White M, Sukhatme V, Nasrin N
Diabetes Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Mol Cell Biochem. 1992 Feb 12;109(2):99-105. doi: 10.1007/BF00229762.
In ongoing studies aimed at elucidating the mechanism of insulin action on the expression of genes that modulate glucose utilization and cell growth, we have focused on the inductive effect of insulin on transcription of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the early growth response gene, Egr-1. Insulin acutely stimulates the expression of both genes in 3T3 adipocytes; however, in primary adipocytes, chronic insulin exposure has opposing effects on the expression of these genes. GAPDH mRNA is decreased in the epididymal fat cells of diabetic animals and is increased over control levels when insulin is replaced, while Egr-1 mRNA levels are increased in diabetic animals. These observations, coupled with the finding that insulin-stimulated Egr-1 gene transcription is impaired in a Chinese hamster ovarian (CHO) cell line that displays normal metabolic responses but impaired ability to regulate DNA synthesis, support the conclusion that insulin regulation of Egr-1, a growth response gene, and GAPDH, a metabolic response gene, are mediated by distinct pathways. We present evidence that supports the role of protein phosphorylation in mediating the effect of insulin on activation of Egr-1 and GAPDH gene transcription.
在旨在阐明胰岛素对调节葡萄糖利用和细胞生长的基因表达作用机制的正在进行的研究中，我们聚焦于胰岛素对甘油醛-3-磷酸脱氢酶（GAPDH）和早期生长反应基因Egr-1转录的诱导作用。胰岛素能在3T3脂肪细胞中急性刺激这两个基因的表达；然而，在原代脂肪细胞中，长期暴露于胰岛素对这些基因的表达有相反的影响。糖尿病动物附睾脂肪细胞中的GAPDH mRNA减少，而在补充胰岛素后其水平高于对照水平，而糖尿病动物中的Egr-1 mRNA水平升高。这些观察结果，再加上在一个中国仓鼠卵巢（CHO）细胞系中发现胰岛素刺激的Egr-1基因转录受损，该细胞系显示出正常的代谢反应但调节DNA合成的能力受损，支持了这样的结论：胰岛素对生长反应基因Egr-1和代谢反应基因GAPDH的调节是由不同途径介导的。我们提供的证据支持蛋白质磷酸化在介导胰岛素对Egr-1和GAPDH基因转录激活作用中的作用。
