PMID- 36982168
OWN - NLM
STAT- MEDLINE
DCOM- 20230330
LR  - 20231213
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 6
DP  - 2023 Mar 7
TI  - Muscle Cell Insulin Resistance Is Attenuated by Rosmarinic Acid: Elucidating the 
      Mechanisms Involved.
LID - 10.3390/ijms24065094 [doi]
LID - 5094
AB  - Obesity and elevated blood free fatty acid (FFA) levels lead to impaired insulin 
      action causing insulin resistance in skeletal muscle, and contributing to the 
      development of type 2 diabetes mellitus (T2DM). Mechanistically, insulin 
      resistance is associated with increased serine phosphorylation of the insulin 
      receptor substrate (IRS) mediated by serine/threonine kinases including mTOR and 
      p70S6K. Evidence demonstrated that activation of the energy sensor AMP-activated 
      protein kinase (AMPK) may be an attractive target to counteract insulin 
      resistance. We reported previously that rosemary extract (RE) and the RE 
      polyphenol carnosic acid (CA) activated AMPK and counteracted the FFA-induced 
      insulin resistance in muscle cells. The effect of rosmarinic acid (RA), another 
      polyphenolic constituent of RE, on FFA-induced muscle insulin resistance has 
      never been examined and is the focus of the current study. Muscle cell (L6) 
      exposure to FFA palmitate resulted in increased serine phosphorylation of IRS-1 
      and reduced insulin-mediated (i) Akt activation, (ii) GLUT4 glucose transporter 
      translocation, and (iii) glucose uptake. Notably, RA treatment abolished these 
      effects, and restored the insulin-stimulated glucose uptake. Palmitate treatment 
      increased the phosphorylation/activation of mTOR and p70S6K, kinases known to be 
      involved in insulin resistance and RA significantly reduced these effects. RA 
      increased the phosphorylation of AMPK, even in the presence of palmitate. Our 
      data indicate that RA has the potential to counteract the palmitate-induced 
      insulin resistance in muscle cells, and further studies are required to explore 
      its antidiabetic properties.
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 - 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 - 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  - RGPIN-2018-06666/Natural Sciences and Engineering Research Council/
PT  - Journal Article
DEP - 20230307
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Insulin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Palmitates)
SB  - IM
MH  - Humans
MH  - *Insulin Resistance/physiology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - AMP-Activated Protein Kinases/metabolism
MH  - *Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Glucose/metabolism
MH  - Muscle, Skeletal/metabolism
MH  - Insulin/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Muscle Cells/metabolism
MH  - Phosphorylation
MH  - Palmitates/metabolism
MH  - Rosmarinic Acid
PMC - PMC10049470
OTO - NOTNLM
OT  - AMPK
OT  - GLUT4
OT  - IRS-1
OT  - free fatty acid
OT  - insulin resistance
OT  - muscle
OT  - palmitate
OT  - rosmarinic acid
COIS- The authors declare no conflict of interest.
EDAT- 2023/03/30 06:00
MHDA- 2023/03/30 06:11
PMCR- 2023/03/07
CRDT- 2023/03/29 01:35
PHST- 2022/11/08 00:00 [received]
PHST- 2023/01/16 00:00 [revised]
PHST- 2023/01/26 00:00 [accepted]
PHST- 2023/03/30 06:11 [medline]
PHST- 2023/03/29 01:35 [entrez]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/03/07 00:00 [pmc-release]
AID - ijms24065094 [pii]
AID - ijms-24-05094 [pii]
AID - 10.3390/ijms24065094 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Mar 7;24(6):5094. doi: 10.3390/ijms24065094.