OVEREXPRESSION OF GLUCOSE TRANSPORTERS IN RAT MESANGIAL CELLS CULTURED IN A NORMAL GLUCOSE MILIEU MIMICS THE DIABETIC PHENOTYPE
OVEREXPRESSION OF GLUCOSE TRANSPORTERS IN RAT MESANGIAL CELLS CULTURED IN A NORMAL GLUCOSE MILIEU MIMICS THE DIABETIC PHENOTYPE
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DOI：
10.1172/jci118226
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发表时间：
1995-10-01
影响因子：
15.9
通讯作者：
GRONDIN, JM
中科院分区：
文献类型：
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作者：
HEILIG, CW;CONCEPCION, LA;GRONDIN, JM
高葡萄糖浓度的环境刺激系膜细胞（MC）培养中细胞外基质（ECM）的合成，这可能是由细胞内葡萄糖浓度的类似增加引起的。我们推测，增加的摄取，而不是葡萄糖浓度本身，是ECM形成夸大的主要决定因素。我们比较了35 mM葡萄糖对正常MCs中ECM合成的影响和8 mM葡萄糖对过表达葡萄糖转运体GLUT1 （MCGT1）的相同细胞的影响。将培养基葡萄糖从8 mM增加到35 mM，导致正常MCs增加总胶原合成和分解代谢，净积累增加81-90%，与细菌β -半乳糖苷酶（MCLacZ）转导的对照MCs相比，在8 mM葡萄糖中生长的人GLUT1基因（MCGT1）转导的MCs的GLUT1蛋白表达量增加10倍，细胞肌醇、乳酸生成和山梨糖醇含量分别增加1.9倍、2.1倍和2.5倍。与MCLacZ相比，MCGT1还表现出葡萄糖摄取（5倍）和净利用率（43倍）的增加，以及单个ECM成分的更多合成。此外，总胶原合成和分解代谢也增强，净胶原积累比对照组增加111-118%，因此，葡萄糖转运活性是MCs形成ECM的重要调节因子；高细胞外葡萄糖浓度的存在并不是刺激基质合成所必需的。
An environment of high glucose concentration stimulates the synthesis of extracellular matrix (ECM) in mesangial cell (MC) cultures, This may result from a similar increase in intracellular glucose concentration, We theorized that increased uptake, rather than glucose concentration per se is the major determinant of exaggerated ECM formation, To test this, we compared the effects of 35 mM glucose on ECM synthesis in normal MCs with those of 8 mM glucose in the same cells overexpressing the glucose transporter GLUT1 (MCGT1). Increasing medium glucose from 8 to 35 mM caused normal MCs to increase total collagen synthesis and catabolism, with a net 81-90% increase in accumulation, MCs transduced with the human GLUT1 gene (MCGT1) grown in 8 mM glucose had a 10-fold greater GLUT1 protein expression and a 1.9, 2.1, and 2.5-fold increase in cell myo-inositol, lactate production, and cell sorbitol content, respectively, as compared to control MCs transduced with bacterial beta-galactosidase (MCLacZ). MCGT1 also demonstrated increased glucose uptake (5-fold) and increased net utilization (43-fold), and greater synthesis of individual ECM components than MCLacZ. In addition, total collagen synthesis and catabolism were also enhanced with a net collagen accumulation 111-118% greater than controls, Thus, glucose transport activity is an important modulator of ECM formation by MCs; the presence of high extracellular glucose concentrations is not necessarily required for the stimulation of matrix synthesis.