{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T02:45:52Z","timestamp":1761965152902,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T00:00:00Z","timestamp":1578614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI12\/00338"],"award-info":[{"award-number":["PI12\/00338"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Little is known about the jejunal insulin signalling pathways in insulin resistance\/diabetes states and their possible regulation by insulin\/leptin. We study in jejunum the relation between insulin signalling and insulin resistance in morbidly obese subjects with low (MO-low-IR) or with high insulin resistance (MO-high-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM), and the effect of insulin\/leptin on intestinal epithelial cells (IEC). Insulin receptor substrate-1 (IRS1) and the catalytic p110\u03b2 subunit (p110\u03b2) of phosphatidylinositol 3-kinase (PI3K) were higher in MO-high-IR than in MO-low-IR. The regulatory p85\u03b1 subunit of PI3K (p85\u03b1)\/p110\u03b2 ratio was lower in MO-high-IR and MO-metf-T2DM than in MO-low-IR. Akt-phosphorylation in Ser473 was reduced in MO-high-IR compared with MO-low-IR. IRS1 and p110-\u03b2 were associated with insulin and leptin levels. The improvement of body mass index (BMI) and HOMA-IR (homeostasis model assessment of insulin resistance index) after bariatric surgery was associated with a higher IRS1 and a lower p85\u03b1\/p110\u03b2 ratio. IEC (intestinal epithelial cells) incubation with a high glucose + insulin dose produced an increase of p85\u03b1 and p110\u03b2. High dose of leptin produced an increase of IRS1, p85\u03b1 and p110\u03b2. In conclusion, despite the existence of insulin resistance, the jejunal expression of genes involved in insulin signalling was increased in MO-high-IR. Their expressions were regulated mainly by leptin. IRS1 and p85\u03b1\/p110\u03b2 ratio was associated with the evolution of insulin resistance after bariatric surgery.<\/jats:p>","DOI":"10.3390\/jcm9010196","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T04:05:51Z","timestamp":1578888351000},"page":"196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Jejunal Insulin Signalling Is Increased in Morbidly Obese Subjects with High Insulin Resistance and Is Regulated by Insulin and Leptin"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5842-8873","authenticated-orcid":false,"given":"Carolina","family":"Gutierrez-Repiso","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Universitario Virgen de la Victoria, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ailec","family":"Ho-Plagaro","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29009 M\u00e1laga, Spain"},{"name":"Facultad de Ciencias, Universidad de M\u00e1laga, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concepci\u00f3n","family":"Santiago-Fernandez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29009 M\u00e1laga, Spain"},{"name":"Facultad de Medicina, Universidad de M\u00e1laga, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Garcia-Serrano","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Regional Universitario, 29009 M\u00e1laga, Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas-CIBERDEM, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"Rodr\u00edguez-Pacheco","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Valdes","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Regional Universitario, 29009 M\u00e1laga, Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas-CIBERDEM, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes","family":"Garrido-Sanchez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Universitario Virgen de la Victoria, 29009 M\u00e1laga, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n-CIBEROBN, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Rodr\u00edguez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"L\u00f3pez-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco J.","family":"Moreno-Ruiz","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Cirug\u00eda General, Digestiva y Trasplantes, Hospital Regional Universitario, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Alcain-Martinez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amandine","family":"Gautier-Stein","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1213, F-69008 Lyon, France"},{"name":"Universit\u00e9 de Lyon, F-69008 Lyon, France"},{"name":"Facult\u00e9 Lyon-Est Laennec, Universit\u00e9 de Lyon 1, F-69622 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Mithieux","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1213, F-69008 Lyon, France"},{"name":"Universit\u00e9 de Lyon, F-69008 Lyon, France"},{"name":"Facult\u00e9 Lyon-Est Laennec, Universit\u00e9 de Lyon 1, F-69622 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3491-2724","authenticated-orcid":false,"given":"Eduardo","family":"Garcia-Fuentes","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga-IBIMA, 29009 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29009 M\u00e1laga, Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas-CIBERDEM, 29009 M\u00e1laga, 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