Chikusetsu saponin IVa regulates glucose uptake and fatty acid oxidation: implications in antihyperglycemic and hypolipidemic effects. (12th February 2015)

• Record Type: Journal Article
• Authors: Li, Yuwen; Zhang, Tiejun; Cui, Jia; Jia, Na; Wu, Yin; Xi, Miaomiao; Wen, Aidong
• Is Part Of: Journal of pharmacy and pharmacology. Volume 67:Number 7(2015:Jul.)
• Page Start: 997
• Page End: 1007
• Publication Date: 2015-02-12
• Subjects: Adenosine monophosphate activated protein kinase -- Chikusetsu saponin IVa -- carnitine palmitoyl transferase-1 -- glucose and lipid metabolism -- Glucose transporter 4; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12392
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: Objectives: 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 A ralia 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. Key findings: 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.