Comparative evaluation in treating qi-yin deficiency and phlegm stasis syndrome of type 2 diabetes mellitus in a rat model

Objective:To compare the efficacy of traditional Chinese medicine (TCM),western medicine and integrative medicine in treating type 2 diabetes mellitus (T2DM) in a rat model.Methods:The T2DM rat model was established with a high-fat diet (HFD) for 35 days and a single injection of streptozotocin (STZ,30 mg/kg).The T2DM-induced rats were divided into three groups,and treated with Yiqi Yangyin Huatan (YQYYHT) granules (3.84 g/kg per day),pioglitazone (1.35 mg/kg per day) or YQYYHT granules + pioglitazone (3.84 g/kg per day+1.35 mg/kg per day) respectively for 14 days.Clinical features and behavioral changes,as well as T2DM indicators,were recorded to evaluate therapeutics effects in each treatment group.Results:The T2DM rat model expressed insulin resistance (IR),with features similar to qi-yin deficiency and phlegm stasis syndrome,including decreased cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio,decreased levels of Na+-K+-ATPase,superoxide dismutase (SOD) and high density lipoprotein-cholesterol (HDL-C),and increased levels of serum triglyceride (TG),total cholesterol (TC) and low density lipoprotein (LDL-C).All three treatment groups showed significant decreases in fasting blood glucose (FBG) and fasting insulin (Fins),and improvement of TCM syndrome to different degrees.Importantly,YQYYHT improved the most of the indicators of T2DM,followed by integrative medicine and pioglitazone alone.Conclusion:Compared with western medicine or integrative medicine,prescription of TCM based on syndrome differentiation may offer more advantages in the prevention and treatment of T2DM.

Efficacy of integrative medicine in deficiency of both qi and yin in the rat model of type 2 diabetes

Objective:To establish a rat model of type 2 diabetes(T2DM)manifesting the Chinese medicine syndrome pattern of both qi and yin deficiency for evaluating the efficacy of a Chinese herbal formula(CHF),integrative medicine(IM),and pioglitazone(PIO)on T2DM indicators in the animal model.Methods:The rat model was induced by a high-fat diet(HFD)and streptozotocin(STZ,30 mg/kg).CHF(3.4 g/kg),PIO(2.7 mg/kg),and IM(3.4 g CHF+2.7 mg PIO)were administered to rats once daily for 14 days.Related laboratory parameters were observed.Results:Diabetic rats showed unsmooth fur,alopecia,reduced activity,huddling,somnolence,depression,pale or reddened tongue,damp/dark red tail,and high levels of water and food intake,urine volume,and stool weight,but weakened grip strength.Low levels of serum SOD,Nat-Kt-ATPase,cAMP/cGMP,and a high level of iNOS were observed.Hyperglycemia,hyperinsulinemia,insulin resistance,high levels of serum glucagon/IDE and pancreatic amylin,and low serum and pancreatic SS levels were evident as well.Conclusions:A rat model of T2DM with both qi and yin deficiency was successfully replicated.CHF appeared to be more efficacious than IM and PIO in the rat model of qi and yin deficiency pattern of T2DM,though IM and PIO were each found to have their merits and drawbacks in attenuating T2DM indicators in the rat model.

Yiqi Yangyin and Huatan Quyu granule can improve skeletal muscle energy metabolism in a type 2 diabetic rat model by promoting the AMPK/SIRT/PGC-1α signalling pathway

Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the promotion of the AMPK/SIRT/PGC-1α signalling pathway.Methods:Rats were randomly divided into 4 groups:the normal group,the model group,the YYHQ granule group,and the pioglitazone group.The type 2 diabetic rat model was established by feeding a high-fat diet for 5 weeks along with a single intraperitoneal injection of 30 mg/kg streptozotocin (STZ).After modelling successfully,the appropriate drug was intragastrically administered to diabetic rats for 2 weeks,once per day.The YYHQ granule group was given a dose of 4.8 g/kg body weight per day,the pioglitazone group was given a dose of 1.35 mg/kg body weight per day.The doses for both groups were equivalent to the clinical equivalent dose based on a previous study.Other groups were gavaged with the same amount of saline water.Body weight,food intake,water intake,urine volume and grip strength were recorded weekly.The fasting blood glucose(FBG) was determined weekly using blood glucose test strips.The related glucose and lipid metabolism indexes,e.g.,fasting insulin (Fins),glycated haemoglobin (GHb),HOMA-IR,ISI,triglycerides (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA),were determined using biochemical method.The mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK),peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α),carnitine palmitoyl transterase-1 (CPT-1),Sirtuin 1 (SIRT1),and Sirtuin 3 (SIRT3) were assessed using quantitative real-time PCR (qRT-PCR).The protein expression levels of creatine kinase (CK),Ca2+ ATPase,α-Actin,AMPK,PGC-1α and CPT-1 were determined using enzyme-linked immunosorbent assay method (ELISA).Results:Body weight decreased significantly (P <.01),food intake,water intake and urine volume increased significantly (P <.01),and grip strength decreased significantly (P <.01) in the model group compared with the normal group.The levels of FBG,Fins,GHb and HOMA-IR increased significantly (P <.01),and the ISI decreased significantly (P <.01) in the model group.The levels of TG,TC,LDL-C and FFA increased significantly (P <.05 or P <.01),and the level of HDL-C decreased significantly (P <.05) in the model group.These changes were reversed after treatment with YYHQ granule or pioglitazone.Compared with the model group,the YYHQ granule and pioglitazone groups significantly improve body weight,water intake and urine volume (P <.05 or P <.01),however,both treatments had no significant effect on food intake (P >.05).The levels of FBG,Fins,GHb,HOMA-IR and ISI were improved significantly (P <.01) and the levels of TG,TC and LDL-C were improved significantly (P <.05 or P <.01),however,both treatments had no significant effect on the levels of HDL-C and FFA (P >.05).Further results indicated that YYHQ granule significantly decreased the mRNA expression of AMPK,PGC-1α,CPT-1,SIRT1 and SIRT3 in skeletal muscle (P <.01) and the pioglitazone group showed similar effects;moreover,the protein expression levels of CK,Ca2+ATPase,α-Actin,AMPK,PGC-1α and CPT-1 in skeletal muscle significantly decreased (P <.01),however,pioglitazone had no significant effect on CK and α-Actin (P >.05).Conclusion:The possible molecular mechanism of YYHQ granule improving skeletal muscle insulin resistance in a type 2 diabetic rat model may be related to the stimulation of energy metabolism in skeletal muscle via the AMPK/SIRT/PGC-1α signalling pathway.