Glucosamine regulation of glucose metabolism in cultured human skeletal muscle cells: Divergent effects on glucose transport/phosphorylation and glycogen synthase in non-diabetic and type 2 diabetic subjects
Glucosamine regulation of glucose metabolism in cultured human skeletal muscle cells: Divergent effects on glucose transport/phosphorylation and glycogen synthase in non-diabetic and type 2 diabetic subjects
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DOI：
10.1210/en.140.9.3971
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发表时间：
1999-09-01
期刊：
影响因子：
4.8
通讯作者：
Henry, RR
中科院分区：
文献类型：
--
作者：
Ciaraldi, TP;Carter, L;Henry, RR
长期暴露（48小时）葡萄糖胺导致非糖尿病和2型糖尿病受试者的人类骨骼肌细胞培养物中基础和胰岛素刺激的葡萄糖摄取活性呈剂量依赖性降低。胰岛素摄取反应性也降低。 GLUT1、GLUT3 或 GLUT4 蛋白的总膜表达没有变化。虽然氨基葡萄糖处理对细胞提取物中测量的己糖激酶活性没有显着影响，但完整细胞中的葡萄糖磷酸化在处理后受到损害。在葡萄糖转运和磷酸化下调的条件下，葡萄糖胺处理增加了糖原合成酶的分数速度（FV）。糖原合酶的总活性和蛋白质表达均不受葡萄糖胺处理的影响。葡萄糖胺对糖原合成酶的刺激并不完全是由于可溶性介质。葡萄糖胺处理后总糖原含量和净糖原合成减少，反映了对运输/磷酸化的影响。这些效应在非糖尿病细胞和 2 型细胞中相似。总结： 1) 葡萄糖胺的长期治疗会减少培养的骨骼肌细胞中葡萄糖的转运/磷酸化和糖原的储存，并损害胰岛素反应性。 2) 葡萄糖转运/磷酸化的下调发生在 GLUT 的翻译后水平。 3) 糖原合酶活性随着葡萄糖胺处理而增加。 4) 非糖尿病肌细胞和 2 型肌细胞对葡萄糖胺表现出相同的敏感性和反应性。骨骼肌对葡萄糖胺（己糖胺途径的底物/前体）的暴露增加，会改变多个部位的细胞内葡萄糖代谢，并可能导致该组织的胰岛素抵抗。
Chronic exposure (48 h) to glucosamine resulted in a dose-dependent reduction of basal and insulin-stimulated glucose uptake activities in human skeletal muscle cell cultures from nondiabetic and type 2 diabetic subjects. Insulin responsiveness of uptake was also reduced. There was no change in total membrane expression of either GLUT1, GLUT3, or GLUT4 proteins. While glucosamine treatment had no significant effects on hexokinase activity measured in cell extracts, glucose phosphorylation in intact cells was impaired after treatment. Under conditions where glucose transport and phosphorylation were down regulated, the fractional velocity (FV) of glycogen synthase was increased by glucosamine treatment. Neither the total activity nor protein expression of glycogen synthase were influenced by glucosamine treatment. The stimulation of glycogen synthase by glucosamine was not due totally to soluble mediators. Reflective of the effects on transport/phosphorylation, total glycogen content and net glycogen synthesis were reduced after glucosamine treatment. These effects were similar in nondiabetic and type 2 cells. In summary: 1) Chronic treatment with glucosamine reduces glucose transport/phosphorylation and storage into glycogen in skeletal muscle cells in culture and impairs insulin responsiveness as well. 2) Down-regulation of glucose transport/phosphorylation occurs at a posttranslational level of GLUTs. 3) Glycogen synthase activity increases with glucosamine treatment. 4) Nondiabetic and type 2 muscle cells display equal sensitivity and responsiveness to glucosamine. Increased exposure of skeletal muscle to glucosamine, a substrate/precursor of the hexosamine pathway, alters intracellular glucose metabolism at multiple sites and can contribute to insulin resistance in this tissue.