PMID- 27401286 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20220410 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 192 DP - 2016 Nov 4 TI - The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus (T2DM) rats with insulin resistance. PG - 382-389 LID - S0378-8741(16)30443-3 [pii] LID - 10.1016/j.jep.2016.07.024 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND 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. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Dai, Bing AU - Dai B AD - The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Shaoshan Road, Changsha, Hunan 410007, China. Electronic address: db0223@163.com. FAU - Wu, Qinxuan AU - Wu Q AD - Changsha Medical University, Changsha, Hunan 410219, China. FAU - Zeng, Chengxi AU - Zeng C AD - Changsha Social Work College, Changsha, Hunan 410000, China. FAU - Zhang, Jiani AU - Zhang J AD - Changsha Medical University, Changsha, Hunan 410219, China. FAU - Cao, Luting AU - Cao L AD - Changsha Medical University, Changsha, Hunan 410219, China. FAU - Xiao, Zizeng AU - Xiao Z AD - Changsha Social Work College, Changsha, Hunan 410000, China. Electronic address: 15570883815@163.com. FAU - Yang, Menglin AU - Yang M AD - Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208. LA - eng PT - Journal Article DEP - 20160709 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs2 protein, rat) RN - 0 (Liuwei Dihuang Decoction) RN - 0 (RNA, Messenger) RN - 5W494URQ81 (Streptozocin) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Biomarkers/blood MH - Blood Glucose/*drug effects/metabolism MH - Diabetes Mellitus, Experimental/blood/chemically induced/*drug therapy/enzymology MH - Diabetes Mellitus, Type 2/blood/chemically induced/*drug therapy/enzymology MH - Drugs, Chinese Herbal/*pharmacology MH - Gene Expression Regulation, Enzymologic MH - Hypoglycemic Agents/*pharmacology MH - Insulin/blood MH - Insulin Receptor Substrate Proteins/genetics/metabolism MH - *Insulin Resistance MH - Liver/*drug effects/enzymology/pathology MH - Male MH - Pancreas/drug effects/enzymology/pathology MH - Phosphatidylinositol 3-Kinase/genetics/*metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/genetics/*metabolism MH - RNA, Messenger/genetics/metabolism MH - Rats, Sprague-Dawley MH - Signal Transduction/drug effects MH - Streptozocin MH - Time Factors OTO - NOTNLM OT - Liuwei Dihuang decoction OT - Loganin(:C(17)H(26)O(10),390.38) OT - Morroniside(C(17)H(26)O(11),402.38) OT - PI3K/Akt signaling pathway OT - Paeonoside(C(23)H(28)O(11), 480.47) OT - Sweroside(C(16)H(22)O(9),358.34) OT - Type 2 diabetes mellitus EDAT- 2016/07/13 06:00 MHDA- 2017/05/16 06:00 CRDT- 2016/07/13 06:00 PHST- 2015/12/10 00:00 [received] PHST- 2016/05/17 00:00 [revised] PHST- 2016/07/07 00:00 [accepted] PHST- 2016/07/13 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2016/07/13 06:00 [entrez] AID - S0378-8741(16)30443-3 [pii] AID - 10.1016/j.jep.2016.07.024 [doi] PST - ppublish SO - J Ethnopharmacol. 2016 Nov 4;192:382-389. doi: 10.1016/j.jep.2016.07.024. Epub 2016 Jul 9.