title: Chikusetsu saponin IVa regulates glucose uptake and fatty acid oxidation: implications in antihyperglycemic and hypolipidemic effects.
abstract: OBJECTIVE
  The aim of this study is to investigate antidiabetic effects and molecular mechanisms of the chemical Chikusetsu saponin IVa (CHS) that isolated from root bark of Aralia taibaiensis, which has multiple pharmacological activity, such as relieving rheumatism, promoting blood circulation to arrest pain and antidiabetic action.
  
  
  METHODS
  Rats with streptozotocin/nicotinamide-induced type 2 diabetes mellitus (T2DM) and insulin-resistant myocytes were used. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) and acetyl-CoA carboxylase were quantified by immunoblotting. Assays of glucose uptake, fatty acid oxidation, glucose transporter 4 (GLUT4) translocation and carnitine palmitoyl transferase-1 (CPT-1) activity were performed.
  
  
  RESULTS
  Chronic oral administration of CHS effectively decreases blood glucose, triglyceride, free fatty acid (FFA) and low density lipoprotein-cholesterol levels in T2DM rats. In both normal and insulin-resistant C2C12 myocytes, CHS activates AMPK, and increases glucose uptake or fatty acid oxidation through enhancing membrane translocation of GLUT4 or CPT-1 activity respectively. Knockdown of AMPK significantly diminishes the effects of CHS on glucose uptake and fatty acid oxidation.
  
  
  CONCLUSIONS
  CHS is a novel AMPK activator that is capable of bypassing defective insulin signalling and could be useful for the treatment of T2DM or other metabolic disorders.
authors: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Yuwen
authors: Y
authors: Li
authors: Department of Pharmacology, Medical College, Chungnam National University, Daejon, South Korea.
authors: Tiejun
authors: T
authors: Zhang
authors: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Jia
authors: J
authors: Cui
authors: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Na
authors: N
authors: Jia
authors: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Yin
authors: Y
authors: Wu
authors: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Miaomiao
authors: M
authors: Xi
authors: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Aidong
authors: A
authors: Wen
mesh_terms: D000818:Animals; D027983:Aralia / Q000737:chemistry; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects*; D024301:Plant Bark / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology*; D013311:Streptozocin / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D012503:Saponins; D014280:Triglycerides; C098580:chikusetsu saponin IVa; D013311:Streptozocin; D009828:Oleanolic Acid; D005947:Glucose
keywords: Adenosine monophosphate activated protein kinase; Chikusetsu saponin IVa; Glucose transporter 4; carnitine palmitoyl transferase-1; glucose and lipid metabolism