在转染的AtT-20细胞中，突变胰岛素原（B10天冬氨酸）从调节性分泌途径部分转向组成型分泌途径。
Partial diversion of a mutant proinsulin (B10 aspartic acid) from the regulated to the constitutive secretory pathway in transfected AtT-20 cells.
作者信息
Gross D J, Halban P A, Kahn C R, Weir G C, Villa-Komaroff L
机构信息
E.P. Joslin Research Laboratory, Joslin Diabetes Center, Boston, MA.
出版信息
Proc Natl Acad Sci U S A. 1989 Jun;86(11):4107-11. doi: 10.1073/pnas.86.11.4107.
Abstract
A patient with type II diabetes associated with hyperproinsulinemia has been shown to have a point mutation in one insulin gene allele, resulting in replacement of histidine with aspartic acid at position 10 of the B-chain. To investigate the basis of the proinsulin processing defect, we introduced an identical mutation in the rat insulin II gene and expressed both the normal and the mutant genes in the AtT-20 pituitary corticotroph cell line. Cells expressing the mutant gene showed increased secretion of proinsulin relative to insulin and rapid release of newly synthesized proinsulin. Moreover, the mutant cell lines did not store the prohormone nor did they release it upon stimulation with secretagogues. These data indicate that a significant fraction of the mutant prohormone is released via the constitutive secretory pathway rather than the regulated pathway, thereby bypassing granule-related processing and regulated release.
摘要
一名患有与高胰岛素原血症相关的II型糖尿病患者，其一个胰岛素基因等位基因存在点突变，导致B链第10位的组氨酸被天冬氨酸取代。为了研究胰岛素原加工缺陷的基础，我们在大鼠胰岛素II基因中引入了相同的突变，并在AtT-20垂体促肾上腺皮质激素细胞系中表达正常基因和突变基因。表达突变基因的细胞相对于胰岛素显示出胰岛素原分泌增加，并且新合成的胰岛素原快速释放。此外，突变细胞系既不储存前激素，在用促分泌剂刺激时也不释放它。这些数据表明，相当一部分突变前激素是通过组成型分泌途径而非调节型途径释放的，从而绕过了与颗粒相关的加工和调节型释放。
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