{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:15:23Z","timestamp":1787062523473,"version":"build-2736575974"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1A2B5B01001547"],"award-info":[{"award-number":["NRF-2020R1A2B5B01001547"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2032-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 \u03b8 (PKC \u03b8) 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-1Ser307 and IRS-1Ser632 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.<\/jats:p>","DOI":"10.1093\/toxres\/tfac055","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T03:23:38Z","timestamp":1661397818000},"page":"774-783","source":"Crossref","is-referenced-by-count":8,"title":["A bioactive component of\n                    <i>Portulaca Oleracea<\/i>\n                    L., HM-chromanone, improves palmitate-induced insulin resistance by inhibiting mTOR\/S6K1 through activation of the AMPK pathway in L6 skeletal muscle cells"],"prefix":"10.1093","volume":"11","author":[{"given":"Jae Eun","family":"Park","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, Pusan National University , 2, Busandaehak-ro 63beon-gil, Geumgeong-gu, Busan 46241, Republic of South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6282-6815","authenticated-orcid":false,"given":"Ji Sook","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Pusan National University , 2, Busandaehak-ro 63beon-gil, Geumgeong-gu, Busan 46241, Republic of South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"issue":"7","key":"2022110110360781200_ref1","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1271\/bbb.120107","article-title":"Palmitate contributes to insulin resistance through downregulation of the Src-mediated phosphorylation of Akt in C2C12 myotubes","volume":"76","author":"Feng","year":"2012","journal-title":"Biosci Biotechnol 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