PMID- 32230718
OWN - NLM
STAT- MEDLINE
DCOM- 20210104
LR  - 20240328
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 12
IP  - 4
DP  - 2020 Mar 27
TI  - Amelioration of High-Insulin-Induced Skeletal Muscle Cell Insulin Resistance by 
      Resveratrol Is Linked to Activation of AMPK and Restoration of GLUT4 
      Translocation.
LID - 10.3390/nu12040914 [doi]
LID - 914
AB  - Insulin resistance, the hallmark of type 2 diabetes mellitus (T2DM), is linked to 
      hyperinsulinemia, which develops to counterbalance initial peripheral hormone 
      resistance. Studies indicate that chronically elevated levels of insulin lead to 
      skeletal muscle insulin resistance by deregulating steps within the insulin 
      signaling cascade. The polyphenol resveratrol (RSV) has been shown to have 
      antidiabetic properties in vitro and in vivo. In the present study, we examined 
      the effect of RSV on high insulin (HI)-induced insulin resistance in skeletal 
      muscle cells in vitro and investigated the mechanisms involved. Parental and 
      GLUT4myc-overexpressing L6 rat skeletal muscle cells were used. 
      [(3)H]2-deoxyglucose (2DG) uptake was measured, and total and phosphorylated 
      levels of specific proteins were examined by immunoblotting. Exposure of L6 cells 
      to HI levels (100 nM) for 24 h decreased the acute-insulin-stimulated 2DG uptake, 
      indicating insulin resistance. HI increased ser(307) and ser(636/639) 
      phosphorylation of IRS-1 (to 184% +/- 12% and 225% +/- 28.9% of control, with p < 
      0.001 and p < 0.01, respectively) and increased the phosphorylation levels of 
      mTOR (174% +/- 6.7% of control, p < 0.01) and p70 S6K (228% +/- 33.5% of control, p < 
      0.01). Treatment with RSV abolished these HI-induced responses. Furthermore, RSV 
      increased the activation of AMPK and restored the insulin-mediated increase in 
      plasma membrane GLUT4 glucose transporter levels. These data suggest that RSV has 
      a potential to counteract the HI-induced muscle insulin resistance.
FAU - Vlavcheski, Filip
AU  - Vlavcheski F
AUID- ORCID: 0000-0001-9615-1775
AD  - Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, 
      Canada.
AD  - Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, 
      Canada.
FAU - Den Hartogh, Danja J
AU  - Den Hartogh DJ
AD  - Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, 
      Canada.
AD  - Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, 
      Canada.
FAU - Giacca, Adria
AU  - Giacca A
AD  - Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
AD  - Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
AD  - Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8T, 
      Canada.
AD  - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON M5G 2C4, 
      Canada.
FAU - Tsiani, Evangelia
AU  - Tsiani E
AD  - Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, 
      Canada.
AD  - Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, 
      Canada.
LA  - eng
GR  - 301047-04,/Natural Sciences and Engineering Research Council of Canada/
PT  - Journal Article
DEP - 20200327
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Cell Line
MH  - Glucose Transporter Type 4/*metabolism
MH  - Insulin/pharmacology
MH  - Insulin Receptor Substrate Proteins/metabolism
MH  - Insulin Resistance/*physiology
MH  - Muscle, Skeletal/*cytology
MH  - Rats
MH  - Resveratrol/*pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC7230755
OTO - NOTNLM
OT  - AMPK
OT  - GLUT4
OT  - IRS-1
OT  - high insulin
OT  - insulin resistance
OT  - mTOR
OT  - p70 S6K
OT  - resveratrol
COIS- The authors declare no conflict of interest.
EDAT- 2020/04/02 06:00
MHDA- 2021/01/05 06:00
PMCR- 2020/04/01
CRDT- 2020/04/02 06:00
PHST- 2020/02/29 00:00 [received]
PHST- 2020/03/17 00:00 [revised]
PHST- 2020/03/23 00:00 [accepted]
PHST- 2020/04/02 06:00 [entrez]
PHST- 2020/04/02 06:00 [pubmed]
PHST- 2021/01/05 06:00 [medline]
PHST- 2020/04/01 00:00 [pmc-release]
AID - nu12040914 [pii]
AID - nutrients-12-00914 [pii]
AID - 10.3390/nu12040914 [doi]
PST - epublish
SO  - Nutrients. 2020 Mar 27;12(4):914. doi: 10.3390/nu12040914.