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eCAM Advance Access originally published online on July 21, 2004
eCAM 2004 1(3):269-276; doi:10.1093/ecam/neh028
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© 2004, the authors Evidenced-based Complementary and Alternative Medicine, Vol. 1, Issue 3 © Oxford University Press 2004; all rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated.

Gosha-jinki-gan (a Herbal Complex) Corrects Abnormal Insulin Signaling

Bolin Qin1,*, Masaru Nagasaki2, Ming Ren3, Gustavo Bajotto1, Yoshiharu Oshida1,2 and Yuzo Sato1,2,*

1Department of Sports Medicine, Graduate School of Medicine, Nagoya University Nagoya, Japan, 2Research Center of Health, Physical Fitness and Sports, Nagoya University Nagoya, Japan, and 3Department of Visual Neuroscience, Graduate School of Medicine, Nagoya University Nagoya, Japan

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)-ß 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-ß 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.

Keywords: Gosha-jinki-gan (GJG) – insulin sensitivity – IRS-1 – tyrosine-phosphorylation

Abbreviations: STZ, streptozotocinGJG, Gosha-jinki-ganIR-ß, insulin receptor-ßIRS-1, insulin receptor substrate-1PI 3-kinase, phosphatidylinositol 3-kinaseMCR, metabolic clearance rate for glucose

*For reprints and all correspondence: Yuzo Sato and Bolin Qin, Research Center of Health, Physical Fitness and Sports, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. Tel: +81-52-789-3949; FAX: +81-52-789-3957. E-mail: bolin{at}med.nagoya-u.ac.jp


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