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In our previous studies, we showed that oral DhHP-6 could reduce blood glucose and improve insulin resistance. To investigate the mechanisms of how DhHP-6 ameliorates oxidative stress and insulin resistance, we established T2DM mouse models and glucosamine-induced HepG2 cell insulin resistance models. The results suggested that DhHP-6 decreased blood glucose, increased antioxidant enzyme activity, and inhibited glycogen synthesis in T2DM mice. In addition, DhHP-6 improved insulin resistance by activating phosphatidylinositol 3-kinase (PI3K)\/AKT, and AMP-activated protein kinase (AMPK) pathway in T2DM mice. Furthermore, DhHP-6 also activated PI3K\/AKT and AMPK pathway in glucosamine-induced HepG2 cells. However, LY294002 did not completely inhibit AKT phosphorylation, and partially inhibited AMPK phosphorylation, whilst compound C only partially reduced AMPK phosphorylation, and also partially inhibited AKT phosphorylation, suggesting that AKT and AMPK interact to improve insulin resistance. Thus, these data suggest that DhHP-6 attenuates insulin resistance via the PI3K\/AKT and AMPK pathway.<\/jats:p>","DOI":"10.1042\/bcj20200402","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T11:46:27Z","timestamp":1591616787000},"page":"2363-2381","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["DhHP-6 ameliorates hepatic oxidative stress and insulin resistance in type 2 diabetes mellitus through the PI3K\/AKT and AMPK pathway"],"prefix":"10.1042","volume":"477","author":[{"given":"Kai","family":"Wang","sequence":"first","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Su","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-4513","authenticated-orcid":false,"given":"Liping","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,6,26]]},"reference":[{"key":"2021112218102112200_BCJ-2020-0402C1","doi-asserted-by":"publisher","first-page":"850","DOI":"10.4239\/wjd.v6.i6.850","article-title":"Diabetes mellitus: the epidemic of the century","volume":"6","year":"2015","journal-title":"World J. 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