title: Ursolic acid increases glucose uptake through the PI3K signaling pathway in adipocytes.
abstract: BACKGROUND
  Ursolic acid (UA), a triterpenoid compound, is reported to have a glucose-lowering effect. However, the mechanisms are not fully understood. Adipose tissue is one of peripheral tissues that collectively control the circulating glucose levels.
  
  
  OBJECTIVE
  The objective of the present study was to determine the effect and further the mechanism of action of UA in adipocytes.
  
  
  RESULTS
  The 3T3-L1 preadipocytes were induced to differentiate and treated with different concentrations of UA. NBD-fluorescent glucose was used as the tracer to measure glucose uptake and Western blotting used to determine the expression and activity of proteins involved in glucose transport. It was found that 2.5, 5 and 10 µM of UA promoted glucose uptake in a dose-dependent manner (17%, 29% and 35%, respectively). 10 µM UA-induced glucose uptake with insulin stimulation was completely blocked by the phosphatidylinositol (PI) 3-kinase (PI3K) inhibitor wortmannin (1 µM), but not by SB203580 (10 µM), the inhibitor of mitogen-activated protein kinase (MAPK), or compound C (2.5 µM), the inhibitor of AMP-activated kinase (AMPK) inhibitor. Furthermore, the downstream protein activities of the PI3K pathway, phosphoinositide-dependent kinase (PDK) and phosphoinositide-dependent serine/threoninekinase (AKT) were increased by 10 µM of UA in the presence of insulin. Interestingly, the activity of AS160 and protein kinase C (PKC) and the expression of glucose transporter 4 (GLUT4) were stimulated by 10 µM of UA under either the basal or insulin-stimulated status. Moreover, the translocation of GLUT4 from cytoplasm to cell membrane was increased by UA but decreased when the PI3K inhibitor was applied.
  
  
  CONCLUSIONS
  Our results suggest that UA stimulates glucose uptake in 3T3-L1 adipocytes through the PI3K pathway, providing important information regarding the mechanism of action of UA for its anti-diabetic effect.
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China; Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, Prince Edward Island, Canada; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, People's Republic of China.
authors.forename: Yonghan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Endocrinology, Third People's Hospital of Yunnan Province, Kunming, Yunnan, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, Prince Edward Island, Canada; Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
authors.forename: Shuocheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, Prince Edward Island, Canada; Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Changhao
authors.initials: C
authors.lastname: Sun
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000890:Anti-Infective Agents; D005947:Glucose; D051275:Glucose Transporter Type 4; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D014315:Triterpenes; D000097245:Ursolic Acid; C495693:Slc2a4 protein, mouse