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A Role of Gene Expression of Aldose Reductase in the Development of Diabetic Complications

醛糖还原酶基因表达在糖尿病并发症发生中的作用

基本信息

批准号：
01570634
负责人：
KIKKAWA Ryuichi
金额：
$ 1.41万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

The accumulation of sorbitol in various tissues has been speculated to play an important role in the development of diabetic complications such as neuropathy, retinopathy, and nephropathy. At the moment, the rate of sorbitol production is understood to be modulated mainly by the amount of glucose, the substrate of aldose reductase, an enzyme to convert glucose to sorbitol. However, the role of aldose reductase itself in the rate of sorbitol production has not been well defined. In this research the gene expression of aldose reductase in rat glomerular mesangial cells was investigated in an attempt to clarify the role of aldose reductase in the regulation of the rate of sorbitol production. Using cDNA (10Q) for rat lens aldose reductase the presence of aldose reductase mRNA was confirmed in these cells. The activity of aldose reductase was markedly increased when mesangial cells were incubated in the medium containing large amount of osmolytes ( plus 300 mOsmoles of NaCL ), indicating that the osmolarity may be the factor to modulate the gene expression of aldose reductase as prevously reported in renal medullary cells. However, neither glucose in high concentration or IGF-I, both increased in diabetes mellitus, was able to alter the activity of aldose reductase. Furthermore, the amount of mRNA for aldose reductase in renal glomeruli was not increased in diabetic rats compared to that of control rats.In summary, the gene expression of aldose reductase is unlikely to modulate the rate of sorbitol production in diabetic state, although some abnormalities in aldose reductaseー or its related gene may exist and cause the different severity of diabetic complications between patient to patient

据推测，山梨醇在各种组织中的积累在糖尿病并发症（如神经病变、视网膜病变和肾病）的发生中起重要作用。目前，山梨糖醇的生产速率主要由葡萄糖的量来调节，葡萄糖是醛糖还原酶的底物，醛糖还原酶是一种将葡萄糖转化为山梨糖醇的酶。然而，醛糖还原酶本身在山梨糖醇生产速率中的作用尚未得到很好的定义。本研究通过对大鼠肾小球系膜细胞醛糖还原酶基因表达的研究，试图阐明醛糖还原酶在调节山梨醇生成速率中的作用。利用大鼠晶状体醛糖还原酶cDNA (10Q)，证实了这些细胞中醛糖还原酶mRNA的存在。当系膜细胞在含有大量渗透液（外加300 mOsmoles NaCL）的培养基中孵养时，醛糖还原酶的活性明显增加，这表明渗透压可能是先前报道的肾髓细胞中醛糖还原酶基因表达的调节因素。然而，高浓度葡萄糖或igf - 1（两者在糖尿病患者中均升高）都不能改变醛糖还原酶的活性。此外，糖尿病大鼠肾小球醛糖还原酶mRNA的表达量与对照组相比没有增加。综上所述，醛糖还原酶的基因表达不太可能调节糖尿病状态下山梨醇的生成速度，尽管醛糖还原酶或其相关基因可能存在一些异常，并导致患者之间糖尿病并发症的严重程度不同

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

仲谷了,吉川隆一,羽田勝計,堀江由佳,堀出直樹,前田士郎,戸川雅樹,古屋大祐,繁田幸男: "糸球体メサンギウム細胞におけるアルド-ス還元酵素mRNAの存在" 日本腎臓学会雑誌. 31. 1337 (1989)

Ryo Nakatani、Ryuichi Yoshikawa、Katsuke Hada、Yuka Horie、Naoki Horide、Shiro Maeda、Masaki Tokawa、Daisuke Furuya、Yukio Shigeta：“肾小球系膜细胞中醛糖还原酶 mRNA 的存在”日本肾病学会杂志 31 .1337（ 1989）