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

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)‐β 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‐β 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.