PMID- 22898769
OWN - NLM
STAT- MEDLINE
DCOM- 20130226
LR  - 20220309
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 55
IP  - 11
DP  - 2012 Nov
TI  - Acute exposure to resveratrol inhibits AMPK activity in human skeletal muscle 
      cells.
PG  - 3051-60
LID - 10.1007/s00125-012-2691-1 [doi]
AB  - AIMS/HYPOTHESIS: Recent studies have suggested resveratrol (RSV) as a new natural 
      therapeutic agent to treat type 2 diabetes and lipid-induced insulin resistance. 
      Here, we investigated whether RSV could reverse palmitate-induced insulin 
      resistance in human primary muscle cells. METHODS: Myotubes obtained from six 
      healthy men (54 +/- 3 years (mean +/- SE), BMI 25.0 +/- 1.7 kg/m(2), fasting plasma 
      glucose concentration (fP-glucose) 5.47 +/- 0.09 mmol/l) were treated for 4 h with 
      100 mumol/l RSV and/or 0.2 mmol/l palmitate, and stimulated with or without 100 
      nmol/l insulin. Assays of glucose uptake, glycogen synthesis, palmitate 
      oxidation, intracellular signalling and AMP-activated protein kinase (AMPK) 
      activity were performed. RESULTS: RSV did not reverse palmitate-induced 
      impairment of glucose metabolism. Surprisingly, RSV decreased glucose uptake and 
      glycogen synthesis in human skeletal muscle cells. Palmitate oxidation and 
      phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase beta (ACCbeta) 
      were inhibited by RSV, and RSV completely blocked the activity of AMPK isoform 
      complexes alpha1/beta2/gamma1 and alpha2/beta2/gamma1 in in-vitro kinase activity assays. Endoplasmic 
      reticulum (ER) stress was increased in response to RSV, as indicated by increased 
      phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) and increased 
      expression of CCAAT/enhancer binding protein homologous protein (CHOP). 
      CONCLUSIONS/INTERPRETATION: Acute exposure to RSV inhibits AMPK activity, 
      fatty-acid oxidation and glucose metabolism in human myotubes.
FAU - Skrobuk, P
AU  - Skrobuk P
AD  - Minerva Foundation Institute for Medical Research, Biomedicum 2U, Tukholmankatu 
      8, Helsinki 00290, Finland.
FAU - von Kraemer, S
AU  - von Kraemer S
FAU - Semenova, M M
AU  - Semenova MM
FAU - Zitting, A
AU  - Zitting A
FAU - Koistinen, H A
AU  - Koistinen HA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120817
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Palmitates)
RN  - 0 (Stilbenes)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - AMP-Activated Protein Kinases/*antagonists & inhibitors/metabolism
MH  - Cell Differentiation/drug effects/physiology
MH  - Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Drug Interactions
MH  - Enzyme Inhibitors/*pharmacology
MH  - Glucose/pharmacokinetics
MH  - Glycogen/biosynthesis
MH  - Humans
MH  - Insulin Resistance/physiology
MH  - Male
MH  - Middle Aged
MH  - Muscle Fibers, Skeletal/cytology/drug effects/*enzymology
MH  - Palmitates/metabolism/pharmacology
MH  - Phosphorylation/drug effects/physiology
MH  - Primary Cell Culture
MH  - Resveratrol
MH  - Signal Transduction/drug effects/physiology
MH  - Stilbenes/*pharmacology
EDAT- 2012/08/18 06:00
MHDA- 2013/02/27 06:00
CRDT- 2012/08/18 06:00
PHST- 2012/04/23 00:00 [received]
PHST- 2012/07/25 00:00 [accepted]
PHST- 2012/08/18 06:00 [entrez]
PHST- 2012/08/18 06:00 [pubmed]
PHST- 2013/02/27 06:00 [medline]
AID - 10.1007/s00125-012-2691-1 [doi]
PST - ppublish
SO  - Diabetologia. 2012 Nov;55(11):3051-60. doi: 10.1007/s00125-012-2691-1. Epub 2012 
      Aug 17.