Anti-Hyperglycemic Effect of Single Administered Gardeniae Fructus in Streptozotocin-Induced Diabetic Mice by Improving Insulin Resistance and Enhancing Glucose Uptake in Skeletal Muscle

Abstract

The mechanisms of Gardeniae Fructus (GF) for anti-hyperglycemic action were demonstrated in streptozotocin (STZ)-diabetic mice. Six hours after single intraperitoneal administration of GF (300 mg/kg) or H2O into 3 hour-fasted STZ-diabetic mice, glucose and insulin tolerances were assessed by intraperitoneal glucose (1.5 g/kg) tolerance test (IPGTT) and intraperitoneal insulin (0.65 U/kg) tolerance test (IPITT), respectively. Effects of GF on insulin signaling pathways in soleus muscle such as glucose uptake, expression of glucose transporter 4 (GLUT4) in the plasma membrane and phosphorylation of Akt (P-Akt) in cytosolic fraction were examined in STZ-diabetic mice. In IPGTT test, GF significantly accelerated clearance of exogenous glucose and its glucose-lowering action was greater than H2O-treated controlin STZ-diabetic mice. GF also promoted an exogenous glucose-increased insulin level in STZ-diabetic mice. In IPITT test, GF decreased glucose level to the greater extent than H2O-treated control in STZ-diabetic mice. Furthermore, GF significantly decreased high HOMA-IR in STZ-diabetic mice from 21.6 ± 2.4 to 12.4 ± 1.9 (mg/dl × μU/ml). These results implied that GF improved insulin resistance in STZ-diabetic mice. GF increased glucose uptake of soleus muscle 1.5 times greater than H2O-treated control in STZ-diabetic mice. GF enlarged insulin (10 nmol/ml)-increased glucose uptake to 1.8 time-greater. Correspondingly, GF increased expression of GLUT4 in the plasma membrane of soleus muscle to 1.4 time-greater, and P-Akt in the cytosolic fraction of soleus muscle to 1.9 time-greater than those in H2O-treated control. In conclusion, the improvement of GF on insulin resistance is associated with the repair of insulin signaling via P-Akt, GLUT4 and glucose uptake pathway in soleus muscle of STZ-diabetic mice.