Thomas T P, Feldman E L, Nakamura J, Kato K, Lien M, Stevens M J, Greene D A
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0354.
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9712-6. doi: 10.1073/pnas.90.20.9712.
Physiological hyperglycemia has been speculated to alter phosphoinositide (PPI; inositol phospholipid) signal transduction in cells prone to diabetic complications by two separate mass-action mechanisms with antiparallel putative effects on diacylglycerol (DAG): (i) sorbitol-induced depletion of myo-inositol leads to diminished PPI synthesis and turnover and DAG release, and (ii) elevated glucose-derived DAG precursors enhance de novo DAG synthesis. Because the first mechanism is mediated by aldose reductase (AR2), which converts glucose to sorbitol, the effects of glucose on basal and stimulated PPI signaling were explored in lines of cultured human retinal pigment epithelial cells differing widely in their basal AR2 gene expression and enzymatic activity. The results suggest that the effects of glucose on PPI signaling vary inversely with the level of AR2 activity and parallel the extent of AR2-induced myo-inositol depletion.
据推测，生理性高血糖可通过两种独立的质量作用机制改变易患糖尿病并发症的细胞中的磷酸肌醇（PPI；肌醇磷脂）信号转导，这两种机制对二酰基甘油（DAG）具有反平行的假定作用：（i）山梨醇诱导的肌醇耗竭导致PPI合成、周转及DAG释放减少，以及（ii）葡萄糖衍生的DAG前体增加导致DAG从头合成增强。由于第一种机制由将葡萄糖转化为山梨醇的醛糖还原酶（AR2）介导，因此在基础AR2基因表达和酶活性差异很大的培养人视网膜色素上皮细胞系中，研究了葡萄糖对基础和刺激的PPI信号传导的影响。结果表明，葡萄糖对PPI信号传导的影响与AR2活性水平呈负相关，并与AR2诱导的肌醇耗竭程度平行。
