胰岛素受体变异性剪接与肿瘤和2型糖尿病

Alternative Splicing of Insulin Receptor mRNA in Cancer and Type 2 Diabetes Mellitus: a Review

胰岛素受体基因第11号外显子因为变异性剪接而形成两种胰岛素受体,两者与配体胰岛素、胰岛素样生长因子的结合力以及分别诱导的信号传导通路、发挥的生物学效应存在显著差异。这种差异不仅可能是导致胰岛素抵抗、2型糖尿病的重要原因,也会影响肿瘤细胞的生长、增殖、抗凋亡。虽然具体的调节机制尚不明确,但高胰岛素血症及高血糖等代谢因素是影响胰岛素受体变异性剪接的重要原因,同时基因序列敲除试验证实,胰岛素受体基因水平的改变会影响胰岛素受体的变异性剪接。

The insulin receptor exists in two isoforms that result from alternative splicing of exon 11 in the primary transcript. The two isoforms have different affinities for insulin and insulin-like growth factors, and mediate different biological actions by different intracellular pathways. Differential expression of the two isoforms not only might contribute to insulin resistance in type 2 diabetes mellitus, but also play an important role in the pathogenesis of cancer. Alternative splicing can be regulated by metabolic and hormonal factors, such as hyperinsulinemia and hyperglycemia, but the precise mechanism is unknown. It has also been demonstrated that there are certain important nucleotide sequences in insulin receptor gene that can influence alternative splicing.