{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T17:41:40Z","timestamp":1769276500565,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":230,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673839"],"award-info":[{"award-number":["81673839"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373507"],"award-info":[{"award-number":["81373507"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>\n                    Berberine (BBR), a natural compound extracted from a Chinese herb, has been shown to effectively attenuate insulin resistance (IR) and inflammation in the clinic. However, its ameliorative mechanism against IR is not well defined. This study is aimed at investigating the effect of BBR and protein phosphatase, Mg\n                    <jats:sup>2+<\/jats:sup>\n                    \/Mn\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent 1B (PPM1B) on IR. Biochemical measurements and liver histopathology were detected using the biochemical analyzer and HE staining in ZDF rats, respectively. Microarray analysis of liver tissues was performed, and differentially expressed gene (DEG) levels were examined by quantitative real\u2010time PCR (qPCR) and Western blot. Additionally, the effect of BBR was also explored in HepG2\u2010IR cells. The glucose oxidase method and the fluorescent glucose analog were used to detect glucose consumption and uptake, respectively. The PKA inhibitor H89, ELISA, qPCR, Western blot, and immunofluorescence staining were employed to estimate the expression levels of related signaling pathways. To evaluate the roles of PPM1B, HepG2\u2010IR cells were stably infected with lentivirus targeting PPM1B. The administration of BBR drastically decreased the body weight, urine volume, blood glucose, blood urea nitrogen (BUN), CHOL, hepatic index levels, and pathologic changes and improved ALB levels in ZDF rats with PPM1B upregulation. Furthermore, BBR effectively improves glucose consumption, uptake, and inflammation in HepG2\u2010IR cells. The knockdown of PPM1B expression aggravated the inflammatory response and glycometabolism disorder in HepG2\u2010IR cells. Mechanistically, a reversal in the expression of cAMP, PKA, PPM1B, PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    , LRP1, GLUT4, NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B p65, JNK, pIKK\n                    <jats:italic>\u03b2<\/jats:italic>\n                    Ser181, IKK\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , IRS\u20101 Ser307, IRS\u20101, IRS\u20102 Ser731, IRS\u20102, PI3K p85, and AKT Ser473 contributes to ameliorate IR in HepG2\u2010IR cells with BBR treatment. Altogether, these results suggest that BBR might regulate IR progression through the regulation of the cAMP, PKA, PPM1B, PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    , LRP1, GLUT4, NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B p65, JNK, pIKK\n                    <jats:italic>\u03b2<\/jats:italic>\n                    Ser181, IKK\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , IRS\u20101 Ser307, IRS\u20101, IRS\u20102 Ser731, IRS\u20102, PI3K p85, and AKT Ser473 expression in the liver.\n                  <\/jats:p>","DOI":"10.1155\/2020\/2141508","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T19:39:54Z","timestamp":1597779594000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Berberine Improves Inflammatory Responses of Diabetes Mellitus in Zucker Diabetic Fatty Rats and Insulin\u2010Resistant HepG2 Cells through the PPM1B Pathway"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5540-768X","authenticated-orcid":false,"given":"Yang Sheng","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6351-6459","authenticated-orcid":false,"given":"Yi Tao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi Jie","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao Jie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6182-7306","authenticated-orcid":false,"given":"Yuan Xiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian Shu","family":"Lou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li Ting","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Ting","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu Ning","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8656-0428","authenticated-orcid":false,"given":"Chang Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3107"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13491"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-14-188"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28898"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2532935"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2925"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2003.10.013"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802501"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.10.088"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-017-0165-7"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19061691"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6217"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-018-0157-8"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016556"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2011.10.008"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2012007500080"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.111.134791"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01229-0"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0341370"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2008.09.012"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306273200"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-6-60"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm415"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1265219"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0166378"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26940"},{"key":"e_1_2_10_27_2","first-page":"68","article-title":"Is type diabetes a chronic inflammatory\/autoimmune disease","volume":"15","author":"Syed M. A.","year":"2002","journal-title":"Diabetes, Nutrition & Metabolism"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135846"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.07.031"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-016-1543-5"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-3271-3_13"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10856"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.05.129"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-4117-4"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121113"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13378"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m109.040428"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5180-14.2015"},{"key":"e_1_2_10_39_2","first-page":"346","article-title":"The adipocyte IKK\/NFkappaB pathway: a therapeutic target for insulin resistance","volume":"10","author":"Ruan H.","year":"2009","journal-title":"Current Opinion in Investigational Drugs"}],"container-title":["Journal of Immunology Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/jir\/2020\/2141508.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/jir\/2020\/2141508.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2020\/2141508","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T14:16:43Z","timestamp":1762093003000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2020\/2141508"}},"subtitle":[],"editor":[{"given":"Tomasz","family":"Baczek","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1155\/2020\/2141508"],"URL":"https:\/\/doi.org\/10.1155\/2020\/2141508","archive":["Portico"],"relation":{},"ISSN":["2314-8861","2314-7156"],"issn-type":[{"value":"2314-8861","type":"print"},{"value":"2314-7156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"2020-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2141508"}}