title: Caulerpa lentillifera extract ameliorates insulin resistance and regulates glucose metabolism in C57BL/KsJ-db/db mice via PI3K/AKT signaling pathway in myocytes.
abstract: BACKGROUND
  Glucose homeostasis is distorted by defects of the PI3K/AKT and AMPK pathways in insulin-sensitive tissues, allowing the accumulation of glucose in the blood. The purpose of this study was to assess the effects and mechanisms by which ethanol extract of Caulerpa lentillifera (CLE) regulates glucose metabolism in C57BL/KsJ-db/db (db/db) mice.
  
  
  METHODS
  Mice were administered CLE (250 or 500 mg/kg BW) or rosiglitazone (RSG, 10 mg/kg BW) for 6 weeks. Then, oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were performed, and blood glucose was measured in db/db mice. Levels of insulin and insulin resistance factors in plasma, glycogen content in the liver, and IRS, PI3K, AKT, and GLUT4 expressions in skeletal muscles were measured in db/db mice. Glucose uptake and insulin signaling molecules were measured in L6 myocytes, using fluorometry and Western blotting.
  
  
  RESULTS
  CLE significantly decreased fasting blood glucose, glucose level in OGTT and IPITT, plasma insulin, homeostatic model assessment-insulin resistant (HOMA-IR), TNF-α, IL-6, FFA, TG and TC levels, and hepatic glycogen content in db/db mice. CLE significantly increased the activation of IRS, AKT, PI3K, and GLUT4, which are the key effector molecules of the PI3K/AKT pathway in L6 myocytes and the skeletal muscles of db/db mice. The enhanced glucose uptake by CLE was abolished by treatment with a PI3K inhibitor (LY294002), but not by an AMPK inhibitor (compound C) in L6 myocytes. CLE regulated glucose uptake and homeostasis via the PI3K/AKT pathway in myocytes and db/db mice, respectively.
  
  
  CONCLUSIONS
  Our results suggest that CLE could be a potential candidate for the prevention of diabetes.
authors.affiliation: Department of Oriental Medicine Resources and Institute of Korean Medicine Industry, Mokpo National University, 1666 Youngsan-ro, Muan-gun, 534-729, Jeonnam, Republic of Korea. bhesh82@gmail.com.
authors.forename: Bhesh Raj
authors.initials: BR
authors.lastname: Sharma
authors.affiliation: College of Pharmacy, Mokpo National University, 534-729, Jeonnam, Republic of Korea. hyunkim@mokpo.ac.kr.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Oriental Medicine Resources and Institute of Korean Medicine Industry, Mokpo National University, 1666 Youngsan-ro, Muan-gun, 534-729, Jeonnam, Republic of Korea. rhyudy@mokpo.ac.kr.|Department of Environmental and Molecular Toxicology, Oregon State University, 97331, Corvallis, OR, USA. rhyudy@mokpo.ac.kr.
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Rhyu
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D046068:Caulerpa / Q000737:chemistry*; D002460:Cell Line; D004032:Diet; D004822:Epididymis / Q000378:metabolism; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D006003:Glycogen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000263:Adenylate Kinase