Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling

• Published in: PloS one Vol. 9; no. 2; p. e87894
• Main Authors: Shen, Yan, Honma, Natsumi, Kobayashi, Katsuya, Jia, Liu Nan, Hosono, Takashi, Shindo, Kazutoshi, Ariga, Toyohiko, Seki, Taiichiro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14-02-2014; Public Library of Science (PLoS)
• Subjects: 3T3-L1 Cells; Acetyl-CoA carboxylase; Activation; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipose tissue; AMP; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Animal tissues; Animals; Biology; Body Weight - drug effects; Cell culture; Cinnamomum; Cinnamomum zeylanicum; Cinnamomum zeylanicum - chemistry; Cinnamon; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Disease Models, Animal; Enzymes; Gene Knockdown Techniques; Glucose; Glucose - metabolism; Glucose tolerance; Glucose tolerance test; Glucose transporter; Glucose Transporter Type 4 - metabolism; In vivo methods and tests; Insulin; Insulin - blood; Insulin Resistance; Kinases; LKB1 protein; Male; Medicine; Mice; Muscle Cells - drug effects; Muscle Cells - metabolism; Muscles; Myocytes; Myotubes; Phosphorylation; Phosphorylation - drug effects; Plant Extracts - administration & dosage; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Protein Kinase Inhibitors - pharmacology; Protein kinases; Protein Transport - drug effects; Protein-Serine-Threonine Kinases - metabolism; Rats; Rats, Inbred OLETF; Ribonucleic acid; RNA; RNA-mediated interference; Rodents; Signal transduction; Signal Transduction - drug effects; Signaling; siRNA; Streptozocin; Studies; Translocation; Type 1 diabetes; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0087894

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.