{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:57:19Z","timestamp":1792090639477,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Control of Innate Immunity Collaborative Innovation Partnership","award":["SIP No. 14533073"],"award-info":[{"award-number":["SIP No. 14533073"]}]},{"name":"Council for Science from Technology and Innovation (CSTI)","award":["SIP No. 14533073"],"award-info":[{"award-number":["SIP No. 14533073"]}]},{"name":"National Agriculture and Food Research Organization (NARO)","award":["SIP No. 14533073"],"award-info":[{"award-number":["SIP No. 14533073"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lipopolysaccharide (LPS), an endotoxin, induces systemic inflammation by injection and is thought to be a causative agent of chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). However, our previous studies found that oral LPS administration does not exacerbate T2DM conditions in KK\/Ay mice, which is the opposite of the response from LPS injection. Therefore, this study aims to confirm that oral LPS administration does not aggravate T2DM and to investigate the possible mechanisms. In this study, KK\/Ay mice with T2DM were orally administered LPS (1 mg\/kg BW\/day) for 8 weeks, and blood glucose parameters before and after oral administration were compared. Abnormal glucose tolerance, insulin resistance progression, and progression of T2DM symptoms were suppressed by oral LPS administration. Furthermore, the expressions of factors involved in insulin signaling, such as insulin receptor, insulin receptor substrate 1, thymoma viral proto-oncogene, and glucose transporter type 4, were upregulated in the adipose tissues of KK\/Ay mice, where this effect was observed. For the first time, oral LPS administration induces the expression of adiponectin in adipose tissues, which is involved in the increased expression of these molecules. Briefly, oral LPS administration may prevent T2DM by inducing an increase in the expressions of insulin signaling-related factors based on adiponectin production in adipose tissues.<\/jats:p>","DOI":"10.3390\/ijms24054619","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T03:00:38Z","timestamp":1677553238000},"page":"4619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Oral Administration of Lipopolysaccharide Enhances Insulin Signaling-Related Factors in the KK\/Ay Mouse Model of Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"24","author":[{"given":"Kazushi","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Control of Innate Immunity, Technology Research Association, Takamatsu 761-0301, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Control of Innate Immunity, Technology Research Association, Takamatsu 761-0301, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Oda","sequence":"additional","affiliation":[{"name":"Control of Innate Immunity, Technology Research Association, Takamatsu 761-0301, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3558-3678","authenticated-orcid":false,"given":"Vindy","family":"Tjendana Tjhin","sequence":"additional","affiliation":[{"name":"Control of Innate Immunity, Technology Research Association, Takamatsu 761-0301, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Inagawa","sequence":"additional","affiliation":[{"name":"Control of Innate Immunity, Technology Research Association, Takamatsu 761-0301, Japan"},{"name":"Research Institute for Healthy Living, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-0841, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen-Ichiro","family":"Soma","sequence":"additional","affiliation":[{"name":"Control of Innate Immunity, Technology Research Association, Takamatsu 761-0301, Japan"},{"name":"Research Institute for Healthy Living, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-0841, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s00424-008-0564-8","article-title":"Endotoxaemia leads to major increases in inflammatory adipokine gene expression in white adipose tissue of mice","volume":"457","author":"Leuwer","year":"2009","journal-title":"Pflug. 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