title: Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling.
abstract: We previously demonstrated that cinnamon extract (CE) ameliorates type 1 diabetes induced by streptozotocin in rats through the up-regulation of glucose transporter 4 (GLUT4) translocation in both muscle and adipose tissues. This present study was aimed at clarifying the detailed mechanism(s) with which CE increases the glucose uptake in vivo and in cell culture systems using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Specific inhibitors of key enzymes in insulin signaling and AMP-activated protein kinase (AMPK) signaling pathways, as well as small interference RNA, were used to examine the role of these kinases in the CE-induced glucose uptake. The results showed that CE stimulated the phosphorylation of AMPK and acetyl-CoA carboxylase. An AMPK inhibitor and LKB1 siRNA blocked the CE-induced glucose uptake. We also found for the first time that insulin suppressed AMPK activation in the adipocyte. To investigate the effect of CE on type 2 diabetes in vivo, we further performed oral glucose tolerance tests and insulin tolerance tests in type 2 diabetes model rats administered with CE. The CE improved glucose tolerance in oral glucose tolerance tests, but not insulin sensitivity in insulin tolerance test. In summary, these results indicate that CE ameliorates type 2 diabetes by inducing GLUT4 translocation via the AMPK signaling pathway. We also found insulin antagonistically regulates the activation of AMPK.
authors.affiliation: Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Honma
authors.affiliation: Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: School of Pharmacy, Nihon University, Chiba, Japan.
authors.forename: Liu Nan
authors.initials: LN
authors.lastname: Jia
authors.affiliation: Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hosono
authors.affiliation: Department of Food and Nutrition, Japan Women's University, Tokyo, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Shindo
authors.affiliation: Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan.
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Ariga
authors.affiliation: Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan.
authors.forename: Taiichiro
authors.initials: T
authors.lastname: Seki
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D020334:Rats, Inbred OLETF; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D005947:Glucose