title: Aspalathin improves hyperglycemia and glucose intolerance in obese diabetic ob/ob mice.
abstract: OBJECTIVE
  Although several researches have demonstrated that rooibos extract has hypoglycemic effect, the role of aspalathin, a main polyphenol in the extract, remains unclear. Our aims were to find specific mechanisms for anti-diabetic action of aspalathin employing a rat skeletal muscle-derived cell line (L6 myocytes) and a rat-derived pancreatic β-cell line (RIN-5F cells) and to investigate its effect in type 2 diabetic model ob/ob mice.
  
  
  METHODS
  We investigated in vitro the effect of aspalathin on the glucose metabolism through the studies on molecular mechanisms of glucose uptake using cultured L6 myotubes. We also measured the antioxidative ability of aspalathin against reactive oxygen species (ROS) generated by artificial advanced glycation end product (AGE) in RIN-5F cells. In vivo, ob/ob mice were fed 0.1 % aspalathin-containing diet for 5 weeks, and the effect of aspalathin on fasting blood glucose level, glucose intolerance, and hepatic gene expression was studied.
  
  
  RESULTS
  Aspalathin dose dependently increased glucose uptake by L6 myotubes and promoted AMP-activated protein kinase (AMPK) phosphorylation. Aspalathin enhanced GLUT4 translocation to plasma membrane in L6 myoblasts and myotubes. In RIN-5F cells, aspalathin suppressed AGE-induced rises in ROS. In vivo, aspalathin significantly suppressed the increase in fasting blood glucose levels and improved glucose intolerance. Furthermore, aspalathin decreased expression of hepatic genes related to gluconeogenesis and lipogenesis.
  
  
  CONCLUSIONS
  Hypoglycemic effect of aspalathin is related to increased GLUT4 translocation to plasma membrane via AMPK activation. In addition, aspalathin reduces the gene expression of hepatic enzymes related to glucose production and lipogenesis. These results strongly suggest that aspalathin has anti-diabetic potential.
authors.affiliation: Department of Applied Life Science, Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Myoung Jin
authors.initials: MJ
authors.lastname: Son
authors.forename: Miki
authors.initials: M
authors.lastname: Minakawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miura
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yagasaki
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D018149:Glucose Intolerance / Q000188:drug therapy*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D050261:Glycogenolysis / Q000187:drug effects; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000097:blood; D050155:Lipogenesis / Q000187:drug effects; D051379:Mice; D008820:Mice, Obese; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D047188:Chalcones; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D017382:Reactive Oxygen Species; C517016:aspalathin; D002784:Cholesterol; D055372:AMP-Activated Protein Kinases