Shikhman Alexander R, Brinson Diana C, Lotz Martin K
Division of Arthritis Research, The Scripps Research Institute, MEM 161, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E980-5. doi: 10.1152/ajpendo.00243.2003. Epub 2004 Jan 28.
Articular cartilage is an avascular, non-insulin-sensitive tissue that utilizes glucose as the main energy source, a precursor for glycosaminoglycan synthesis, and a regulator of gene expression. Facilitated glucose transport represents the first rate-limiting step in glucose metabolism. Previously, we demonstrated that glucose transport in chondrocytes is regulated by proinflammatory cytokines via upregulation of GLUT mRNA and protein expression. The objective of the present study was to determine differences in molecular mechanisms regulating glucose transport in chondrocytes stimulated with the anabolic transforming growth factor-beta1 (TGF-beta1) vs. the catabolic and proinflammatory cytokine IL-1beta. Both TGF-beta1 and IL-1beta accelerate glucose transport in chondrocytes. Although both IL-1beta and TGF-beta1 enhance glucose transport in chondrocytes to a similar magnitude, IL-1beta induces significantly higher levels of lactate. TGF-beta1-stimulated glucose transport is not associated with increased expression or membrane incorporation of GLUT1, -3, -6, -8, and -10 and depends on PKC and ERK activation. In contrast, IL-1beta-stimulated glucose transport is accompanied by increased expression and membrane incorporation of GLUT1 and -6 and depends upon activation of PKC and p38 MAP kinase. In conclusion, anabolic and catabolic stimuli regulate facilitated glucose transport in human articular chondrocytes via different effector and signaling mechanisms, and they have distinct effects on glycolysis.
关节软骨是一种无血管、对胰岛素不敏感的组织，它利用葡萄糖作为主要能量来源、糖胺聚糖合成的前体以及基因表达的调节剂。易化葡萄糖转运是葡萄糖代谢的第一个限速步骤。此前，我们证明软骨细胞中的葡萄糖转运受促炎细胞因子调控，通过上调葡萄糖转运蛋白（GLUT）的mRNA和蛋白表达来实现。本研究的目的是确定在合成代谢的转化生长因子-β1（TGF-β1）与分解代谢和促炎细胞因子白细胞介素-1β（IL-1β）刺激下，软骨细胞中调节葡萄糖转运的分子机制的差异。TGF-β1和IL-1β均可加速软骨细胞中的葡萄糖转运。虽然IL-1β和TGF-β1均能将软骨细胞中的葡萄糖转运提高到相似程度，但IL-1β诱导的乳酸水平显著更高。TGF-β1刺激的葡萄糖转运与GLUT1、-3、-6、-8和-10的表达增加或膜整合无关，且依赖蛋白激酶C（PKC）和细胞外信号调节激酶（ERK）的激活。相比之下，IL-1β刺激的葡萄糖转运伴随着GLUT1和-6的表达增加及膜整合，且依赖PKC和p38丝裂原活化蛋白激酶（p38 MAP激酶）的激活。总之，合成代谢和分解代谢刺激通过不同的效应器和信号机制调节人关节软骨细胞中的易化葡萄糖转运，并且它们对糖酵解有不同影响。
