title: Synthetic (+)-antroquinonol exhibits dual actions against insulin resistance by triggering AMP kinase and inhibiting dipeptidyl peptidase IV activities.
abstract: OBJECTIVE
  The fungal product (+)-antroquinonol activates AMP kinase (AMPK) activity in cancer cell lines. The present study was conducted to examine whether chemically synthesized (+)-antroquinonol exhibited beneficial metabolic effects in insulin-resistant states by activating AMPK and inhibiting dipeptidyl peptidase IV (DPP IV) activity.
  
  
  METHODS
  Effects of (+)-antroquinonol on DPP IV activity were measured with a DPPIV Assay Kit and effects on GLP-1-induced PKA were measured in AR42J cells. Translocation of the glucose transporter 4, GLUT4, induced either by insulin-dependent PI3K/AKT signalling or by insulin-independent AMPK activation, was assayed in differentiated myotubes. Glucose uptake and GLUT4 translocation were assayed in L6 myocytes. Mice with diet-induced obesity were used to assess effects of acute and chronic treatment with (+)-antroquinonol on glycaemic control in vivo.
  
  
  RESULTS
  The results showed that of (+)-antroquinonol (100 μM ) inhibited the DPP IV activity as effectively as the clinically used inhibitor, sitagliptin. The phosphorylation of AMPK Thr(172) in differentiated myotubes was significantly increased by (+)-antroquinonol. In cells simultaneously treated with S961 (insulin receptor antagonist), insulin and (+)-antroquinonol, the combination of (+)-antroquinonol plus insulin still increased both GLUT4 translocation and glucose uptake. Further, (+)-antroquinonol and sitagliptin reduced blood glucose, when given acutely or chronically to DIO mice.
  
  
  CONCLUSIONS
  Chemically synthesized (+)-antroquinonol exhibits dual effects to ameliorate insulin resistance, by increasing AMPK activity and GLUT4 translocation, along with inhibiting DPP IV activity.
authors: Institute of Biotechnology, National Dong-Hwa University, Hualien, Taiwan; Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
authors: C Y
authors: CY
authors: Hsu
authors: R S
authors: RS
authors: Sulake
authors: P-K
authors: PK
authors: Huang
authors: H-Y
authors: HY
authors: Shih
authors: H-W
authors: HW
authors: Sie
authors: Y-K
authors: YK
authors: Lai
authors: C
authors: C
authors: Chen
authors: C F
authors: CF
authors: Weng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D051379:Mice; D009765:Obesity / Q000378:metabolism; D051381:Rats; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D051275:Glucose Transporter Type 4; C495693:Slc2a4 protein, mouse; D014451:Ubiquinone; D052216:Glucagon-Like Peptide 1; C545357:antroquinonol; D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases; D018819:Dipeptidyl Peptidase 4; D005947:Glucose