title: The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus (T2DM) rats with insulin resistance.
abstract: BACKGROUND
  Liuwei Dihaung decoction (LWDHT) is a well-known classic traditional Chinese medicine formula, consists of six herbs including Rehmannia glutinosa Libosch.(family: Scrophulariaceae), Cornus officinalis Sieb.(family: Cornaceae), Dioscorea opposite Thunb.(family: Dioscoreaceae), Alisma orientale(G. Samuelsson) Juz (family: Alismataceae), Poria cocos (Schw.) Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has been used in the treatment of many types of diseases with signs of deficiency of Yin in the kidneys in China clinically. This study is aimed at investigating the effect of Liuwei dihuang decoction on PI3K/Akt signaling pathway in liver of T2DM rats with insulin resistance.
  
  
  METHODS
  T2DM model was induced in male Sprague-Dawley (SD) rats by high sugar and high fat diets combined with small dose of streptozocin (STZ) injection. The successful T2DM rats were randomly allocated three group--vehicle group, positive control group and Liuwei Dihuang decoction group. After 12-weeks treatment with distilled water, rosiglitazone and LWDHT by intragastric administration respectively, the rats were put to death in batches. The variance of fasting blood glucose (FBG) and fasting insulin (FINS) in serum were determined, the pathological changes of each rats' liver were observed by hematoxylin-eosin (HE) staining, the expression of insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinas B (Akt) involving the canonical PI3K/Akt signaling pathway were detected by Real-time fluorescent quantitative PCR (RT-PCR), and the expression level of IRS2, PI3K, Akt protein and phosphorylated IRS2, PI3K, Akt protein were evaluated by Western Blot. All the data were analyzed by SPSS 17.0.
  
  
  RESULTS
  Four weeks of treatment with LWDHT could significantly decrease the level of FBG and FINS in serum, improve the cellular morphology of liver, kidney, pancreas tissue, and the expression of IRS2, PI3K, Akt mRNA and phosphorylated IRS2, PI3K, Akt protein involved in the canonical PI3K/Akt signaling pathway of T2DM rats in liver were significantly up-regulated, while the total IRS2, PI3K, and Akt protein had no obvious changes.
  
  
  CONCLUSIONS
  The results suggest that Liuwei Dihuang decoction could intervene insulin resistance of T2DM, in part, through regulation of canonical PI3K/Akt signaling pathway of T2DM rats in liver.
authors.affiliation: The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Shaoshan Road, Changsha, Hunan 410007, China. Electronic address: db0223@163.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Dai
authors.affiliation: Changsha Medical University, Changsha, Hunan 410219, China.
authors.forename: Qinxuan
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Changsha Social Work College, Changsha, Hunan 410000, China.
authors.forename: Chengxi
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Changsha Medical University, Changsha, Hunan 410219, China.
authors.forename: Jiani
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Changsha Medical University, Changsha, Hunan 410219, China.
authors.forename: Luting
authors.initials: L
authors.lastname: Cao
authors.affiliation: Changsha Social Work College, Changsha, Hunan 410000, China. Electronic address: 15570883815@163.com.
authors.forename: Zizeng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208.
authors.forename: Menglin
authors.initials: M
authors.lastname: Yang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526299:Irs2 protein, rat; C042579:Liuwei Dihuang Decoction; D012333:RNA, Messenger; D013311:Streptozocin; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: Liuwei Dihuang decoction; Loganin(:C(17)H(26)O(10),390.38); Morroniside(C(17)H(26)O(11),402.38); PI3K/Akt signaling pathway; Paeonoside(C(23)H(28)O(11), 480.47); Sweroside(C(16)H(22)O(9),358.34); Type 2 diabetes mellitus