RRC ID 44921
Author Shen Y, Honma N, Kobayashi K, Jia LN, Hosono T, Shindo K, Ariga T, Seki T.
Title Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling.
Journal PLoS ONE
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.
Volume 9(2)
Pages e87894
Published 2014
DOI 10.1371/journal.pone.0087894
PII PONE-D-13-39530
PMID 24551069
PMC PMC3925101
MeSH 3T3-L1 Cells AMP-Activated Protein Kinases / metabolism* Adipocytes / drug effects Adipocytes / metabolism* Animals Body Weight / drug effects Cinnamomum zeylanicum / chemistry* Diabetes Mellitus, Type 2 / blood Diabetes Mellitus, Type 2 / drug therapy Diabetes Mellitus, Type 2 / metabolism Diabetes Mellitus, Type 2 / pathology Disease Models, Animal Gene Knockdown Techniques Glucose / metabolism* Glucose Transporter Type 4 / metabolism Insulin / blood Insulin Resistance Male Mice Muscle Cells / drug effects Muscle Cells / metabolism* Phosphorylation / drug effects Plant Extracts / administration & dosage Plant Extracts / pharmacology* Plant Extracts / therapeutic use Protein Kinase Inhibitors / pharmacology Protein Transport / drug effects Protein-Serine-Threonine Kinases / metabolism* Rats Rats, Inbred OLETF Signal Transduction / drug effects
IF 2.766
Times Cited 23
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells