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eCAM Advance Access published online on July 21, 2004
eCAM, doi:10.1093/ecam/neh028
Copyright © 2004 by the Oxford University Press.
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Received December 19, 2003
Accepted March 24, 2004

Original Article

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

Bolin Qin 1, Masaru Nagasaki 2, Ming Ren 3, Gustavo Bajotto 1, Yoshiharu Oshida 4, Yuzo Sato 4*

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

* To whom correspondence should be addressed. E-mail: bolin{at}med.nagoya-u.ac.jp.


  Abstract

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.

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