Gosha-jinki-gan (a Herbal Complex) Corrects Abnormal Insulin Signaling
Gosha-jinki-gan (a Herbal Complex) Corrects Abnormal Insulin Signaling
复制标题
DOI：
10.1093/ecam/neh028
复制
发表时间：
2004-01-01
影响因子：
--
通讯作者：
Sato, Yuzo
中科院分区：
文献类型：
--
作者：
Qin, Bolin;Nagasaki, Masaru;Sato, Yuzo
以前的研究表明，传统的草药复合物Gosha-jinki-gan（GJG）改善糖尿病神经病变和胰岛素抵抗。本研究旨在阐明GJG给药对体内胰岛素作用的长期影响以及链脲佐菌素（STZ）糖尿病骨骼肌胰岛素信号传导的早期步骤的分子机制。将大鼠随机分为5个亚组：（1）生理盐水处理对照组，（2）GJG处理对照组，（3）2单位胰岛素+生理盐水处理糖尿病组，（4）生理盐水+ GJG处理糖尿病组和（5）2单位胰岛素+ GJG处理糖尿病组。治疗7天后，在禁食过夜的大鼠中以6 mU/kg/min的胰岛素输注速率进行正葡萄糖钳夹实验。尽管使用2单位胰岛素治疗，与对照组相比，糖尿病大鼠的MCR（ml/kg/min）显著降低（11.4 ± 1.0 vs 44.1 ± 1.5;胰岛素联合GJG或GJG单用组的疗效分别为26 +/- 3.2和24.6 +/- 2.2，P < 0.01。胰岛素与固精颗粒联合给药对糖尿病大鼠骨骼肌中胰岛素受体（IR）-β蛋白含量的增加无影响。然而，降低胰岛素受体底物-1（IRS-1）蛋白含量显着改善治疗与GJG。此外，胰岛素联合GJG治疗糖尿病时，IR-β和IRS-1酪氨酸磷酸化水平的增加被显著抑制。目前的结果表明，改善受损的胰岛素敏感性STZ糖尿病大鼠的GJG管理可能是由于，至少部分，纠正骨骼肌中的胰岛素信号的异常早期步骤。
Previous studies have shown that the traditional herbal complex Gosha-jinki-gan (GJG) improves diabetic neuropathy and insulin resistance. The present study was undertaken to elucidate the molecular mechanisms related with the long-term effects of GJG administration on insulin action in vivo and the early steps of insulin signaling in skeletal muscle in streptozotocin (STZ) diabetes. Rats were randomized into five subgroups: ( 1) saline treated control, ( 2) GJG treated control, ( 3) 2-unit insulin + saline treated diabetic, ( 4) saline + GJG treated diabetic and ( 5) 2-unit insulin + GJG treated diabetic groups. After seven days of treatment, euglycemic clamp experiment at an insulin infusion rate of 6 mU/kg/min was performed in overnight fasted rats. Despite the 2-unit insulin treatment, the metabolic clearance rates of glucose (MCR, ml/kg/min) in diabetic rats were significantly lower compared with the controls (11.4 +/- 1.0 vs 44.1 +/- 1.5; P < 0.001), and were significantly improved by insulin combined with GJG or GJG alone (26 +/- 3.2 and 24.6 +/- 2.2, P < 0.01, respectively). The increased insulin receptor (IR)-beta protein content in skeletal muscle of diabetic rats was not affected by insulin combined with GJG administration. However, the decreased insulin receptor substrate-1 (IRS-1) protein content was significantly improved by treatment with GJG. Additionally, the increased tyrosine phosphorylation levels of IR-beta and IRS-1 were significantly inhibited in insulin combined with GJG treated diabetes. The present results suggest that the improvement of the impaired insulin sensitivity in STZ-diabetic rats by administration of GJG may be due, at least in part, to correction in the abnormal early steps of insulin signaling in skeletal muscle.