PMID- 30885574
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20190909
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 853
DP  - 2019 Jun 15
TI  - Effect of CAPE-pNO(2) against type 2 diabetes mellitus via the AMPK/GLUT4/ 
      GSK3beta/PPARalpha pathway in HFD/STZ-induced diabetic mice.
PG  - 1-10
LID - S0014-2999(19)30182-7 [pii]
LID - 10.1016/j.ejphar.2019.03.027 [doi]
AB  - CAPE-pNO(2), a para-nitro derivative of caffeic acid phenethyl ester (CAPE), has 
      been proved to exert stronger effects on diabetic complications in diabetic mice. 
      The present study aimed at probing into the effect and potential mechanism of 
      CAPE-pNO(2) in type 2 diabetes mellitus (T2DM) compared with CAPE on model 
      animal. Diabetic model was established by feeding one month of high-fat-diet 
      (HFD) before injection of 40 mg/kg streptozotocin (STZ) for five days, and the 
      normal diet mice were set as control group. Model mice were treated by 
      CAPE-pNO(2) for one month again, the levels of blood glucose, blood lipid and 
      blood insulin significantly decreased. In addition, the myocardial enzymes 
      (creatine Kinase and lactate dehydrogenase) and liver transaminase (aspartate 
      aminotransferase and alanine aminotransferase) activities decreased. Furthermore, 
      CAPE-pNO(2) could alleviate pancreatic damage, myocardial injury and hepatic 
      steatosis caused by diabetes mellitus, and significantly improved the islet mass, 
      beta cell survival and the hepatic glycogen content. Besides, CAPE-pNO(2) enhanced 
      the expression of phosphorylation-AMP-activated protein kinas (p-AMPK) (Thr172), 
      GLUT4, peroxisome proliferator-activated receptor-alpha (PPARalpha) and p-Akt (Ser473), 
      and inhibited the expression of glycogen synthase kinase 3beta (GSK3beta) and p-JNK 
      (Thr183/Tyr185) in liver. All of those effects are better than CAPE generally. It 
      suggested that CAPE-pNO(2) ameliorated type 2 diabetes mellitus by effectively 
      protecting islet beta cell and improving the insulin resistance via the 
      AMPK/GLUT4/GSK3beta/PPARalpha pathway.
CI  - Copyright (c) 2019. Published by Elsevier B.V.
FAU - Li, Sai
AU  - Li S
AD  - College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, 
      Beibei, Chongqing 400716, China.
FAU - Huang, Qin
AU  - Huang Q
AD  - College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, 
      Beibei, Chongqing 400716, China.
FAU - Zhang, Liwen
AU  - Zhang L
AD  - College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, 
      Beibei, Chongqing 400716, China.
FAU - Qiao, Xufang
AU  - Qiao X
AD  - College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, 
      Beibei, Chongqing 400716, China.
FAU - Zhang, Yanyan
AU  - Zhang Y
AD  - College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, 
      Beibei, Chongqing 400716, China.
FAU - Tang, Fashu
AU  - Tang F
AD  - College of Animal Science, Southwest University, Rongchang 402460, China.
FAU - Li, Zhubo
AU  - Li Z
AD  - College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, 
      Beibei, Chongqing 400716, China. Electronic address: zb63@swu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20190315
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Blood Glucose)
RN  - 0 (Caffeic Acids)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (PPAR alpha)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - G960R9S5SK (caffeic acid phenethyl ester)
RN  - ML9LGA7468 (Phenylethyl Alcohol)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Body Weight/drug effects
MH  - Caffeic Acids/*chemistry/*pharmacology/therapeutic use
MH  - Diabetes Mellitus, Experimental/*drug therapy/*metabolism/pathology
MH  - Diabetes Mellitus, Type 2/*drug therapy/*metabolism/pathology
MH  - Diet, High-Fat/*adverse effects
MH  - Gene Expression Regulation/drug effects
MH  - Glucose Transporter Type 4/metabolism
MH  - Glycogen/biosynthesis
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - Insulin Resistance
MH  - Insulin-Secreting Cells/drug effects/metabolism
MH  - Liver/drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Myocardium/pathology
MH  - PPAR alpha/metabolism
MH  - Phenylethyl Alcohol/*analogs & derivatives/chemistry/pharmacology/therapeutic use
OTO - NOTNLM
OT  - AMP-activated protein kinas
OT  - Cafeic acid p-nitro-phenethyl ester (CAPE-pNO(2))
OT  - Insulin resistance
OT  - Liver injury
OT  - Type 2 diabetes mellitus
OT  - beta cell
EDAT- 2019/03/20 06:00
MHDA- 2019/09/10 06:00
CRDT- 2019/03/20 06:00
PHST- 2018/12/27 00:00 [received]
PHST- 2019/03/13 00:00 [revised]
PHST- 2019/03/14 00:00 [accepted]
PHST- 2019/03/20 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
PHST- 2019/03/20 06:00 [entrez]
AID - S0014-2999(19)30182-7 [pii]
AID - 10.1016/j.ejphar.2019.03.027 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2019 Jun 15;853:1-10. doi: 10.1016/j.ejphar.2019.03.027. Epub 
      2019 Mar 15.