title: Rhizoma Anemarrhenae extract ameliorates hyperglycemia and insulin resistance via activation of AMP-activated protein kinase in diabetic rodents.
abstract: BACKGROUND
  Rhizoma Anemarrhenae has been used in Asian countries for thousands of years to treat diabetes. Insulin resistance (IR) is the primary cause responsible for type 2 diabetes. The aim of this study was to to assess the hypoglycemic and insulin sensitizing properties of Rhizoma Anemarrhenae extract (TFA) in animal models of insulin resistance and/or diabetes and to delineate modes of action.
  
  
  METHODS
  In-vivo studies were performed on STZ-induced diabetic mice and KK-Ay mice, the former of which were given the extract alone or in combination with insulin for 7 days, and the latter of which were given the extract for 8 consecutive weeks. Fasting blood glucose and serum insulin levels were measured. Pancreatic tissue sections were examined using transmission electron micrographs. Further, hyperinsulinemic-euglycemic clamping study was conducted in BCG vaccine-induced insulin resistance rats, and glucose infusion rate was examined. Mechanisms of action were investigated in 3T3-L1 and Hela cells using Western blot analysis.
  
  
  RESULTS
  Our study showed that TFA enhanced the glucose-lowering effects of exogenous insulin administration in STZ-induced diabetic mice. Therapeutic administration of TFA significantly reduced fasting blood glucose, and serum insulin levels, and markedly increased the size and the number of insulin-producing beta cells in KK-Ay mice. Further, hyperinsulinemic-euglycemic clamping study showed that glucose infusion rate was significantly improved in TFA-treated BCG vaccine-induced insulin resistance rats. Study of mechanism of action revealed that TFA increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in 3T3-L1 cells. It activates AMPK in a LKB1-independent manner, providing a unified explanation for the beneficial effects of TFA.
  
  
  CONCLUSIONS
  This study that TFA mediates activation of AMPK and improves overall glucose and lipid metabolism in diabetic rodents, highlights the potential utility of TFA for the management of type 2 diabetes.
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: New Drug Research Center, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Liang
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
authors.forename: WeiFen
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China. Electronic address: chenwanshengsmmu@aliyun.com.
authors.forename: Wansheng
authors.initials: W
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D031403:Anemarrhena / Q000737:chemistry*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D006367:HeLa Cells; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Animal experiment; Anti-diabetic compounds; Bacillus Calmette-Guérin (PubChem CID: 6451); Carboxymethyl Cellulose Sodium (PubChem CID: 6328154); Compound C (PubChem CID: 11524144); Insulin sensitivity; Mangiferin (PubChem CID: 5281647); Neomangiferin (PubChem CID: 6918448); Pentobarbital Sodium (PubChem CID: 14075609); Pioglitazone (PubChem CID: 4829); STO-609 (PubChem CID: 16760660); Streptozocin (PubChem CID: 29327); Wortmannin (PubChem CID: 312145)