PMID- 36337245
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230827
IS  - 2045-452X (Print)
IS  - 2045-4538 (Electronic)
IS  - 2045-452X (Linking)
VI  - 11
IP  - 5
DP  - 2022 Oct
TI  - A bioactive component of Portulaca Oleracea L., HM-chromanone, improves 
      palmitate-induced insulin resistance by inhibiting mTOR/S6K1 through activation 
      of the AMPK pathway in L6 skeletal muscle cells.
PG  - 774-783
LID - 10.1093/toxres/tfac055 [doi]
AB  - Increased free fatty acid levels in the blood are common in obesity and cause 
      insulin resistance associated with type 2 diabetes in the muscles. Previous 
      studies have confirmed the antidiabetic and anti-obesity potential of 
      (E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone (HM-chromanone). 
      However, it is unknown how HM-chromanone alleviates obesity-related insulin 
      resistance in L6 skeletal muscle cells. Palmitate induced insulin resistance and 
      reduced glucose uptake, whereas HM-chromanone significantly increased glucose 
      uptake. In palmitate-treated L6 skeletal muscle cells, HM-chromanone stimulated 
      liver kinase B1 (LKB1) and 5'-adenosine monophosphate-activated protein kinase 
      (AMPK) phosphorylation. The AMPK inhibitor compound C, and the LKB1 inhibitor 
      radicicol blocked the effects of HM-chromanone. Furthermore, HM-chromanone 
      significantly inhibited mammalian target of rapamycin (mTOR) and ribosomal 
      protein S6 kinase 1 (S6K1) activation, but there was no change in protein kinase 
      C theta (PKC theta) expression. When pAMPK was inhibited with compound C, the effect of 
      HM-chromanone on the inhibition of mTOR and S6K1 was significantly diminished. 
      This indicates that HM-chromanone inhibits mTOR and S6K1 activation through pAMPK 
      activation. Inhibition of mTOR and S6K1 by HM-chromanone significantly reduced 
      IRS-1(Ser307) and IRS-1(Ser632) phosphorylation, leading to insulin resistance. 
      This resulted in an increase in PM-GLUT4 (glucose transporter 4) expression, 
      thereby stimulating glucose uptake in insulin-resistant muscle cells. 
      HM-chromanone can improve palmitate-induced insulin resistance by inhibiting mTOR 
      and S6K1 through activation of the AMPK pathway in L6 skeletal muscle cells. 
      These results show the therapeutic potential of HM-chromanone for improving 
      insulin resistance in type 2 diabetes.
CI  - (c) The Author(s) 2022. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Park, Jae Eun
AU  - Park JE
AD  - Department of Food Science and Nutrition, Pusan National University, 2, 
      Busandaehak-ro 63beon-gil, Geumgeong-gu, Busan 46241, Republic of South Korea.
FAU - Han, Ji Sook
AU  - Han JS
AUID- ORCID: 0000-0002-6282-6815
AD  - Department of Food Science and Nutrition, Pusan National University, 2, 
      Busandaehak-ro 63beon-gil, Geumgeong-gu, Busan 46241, Republic of South Korea.
LA  - eng
PT  - Journal Article
DEP - 20220826
PL  - England
TA  - Toxicol Res (Camb)
JT  - Toxicology research
JID - 101587950
PMC - PMC9618117
OTO - NOTNLM
OT  - AMPK
OT  - HM-chromanone
OT  - homoisoflavonoid
OT  - insulin resistance
OT  - palmitate
EDAT- 2022/11/08 06:00
MHDA- 2022/11/08 06:01
PMCR- 2023/08/26
CRDT- 2022/11/07 04:07
PHST- 2022/04/07 00:00 [received]
PHST- 2022/07/13 00:00 [revised]
PHST- 2022/07/20 00:00 [accepted]
PHST- 2022/11/07 04:07 [entrez]
PHST- 2022/11/08 06:00 [pubmed]
PHST- 2022/11/08 06:01 [medline]
PHST- 2023/08/26 00:00 [pmc-release]
AID - tfac055 [pii]
AID - 10.1093/toxres/tfac055 [doi]
PST - epublish
SO  - Toxicol Res (Camb). 2022 Aug 26;11(5):774-783. doi: 10.1093/toxres/tfac055. 
      eCollection 2022 Oct.