{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:03:56Z","timestamp":1784178236083,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether increased IGFBP-1 following Roux-en-Y gastric bypass (RYGB) surgery is associated with upregulation of IRS-1 and its downstream PI3K\/AKT\/GSK-3\u03b2 signaling components, thereby contributing to the glucose-lowering mechanism of metabolic surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Wild-type C57BL\/6 mice (WT) and C57BL\/6-Igfbpem1 IGFBP-1 knockout mice (KO) were used, along with an induced diabetes model (high-fat diet for 6 weeks followed by low-dose streptozotocin for 5 days prior to surgery). Preoperatively and at 1 to 8 weeks postoperatively, body weight, fasting blood glucose, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR, calculated from fasting glucose and insulin at week 8) were assessed. Plasma samples were collected and stored at -80 \u00b0C. Mice were euthanized at eight weeks postoperatively, and tissues were collected. ELISA was used to measure plasma IGFBP-1, IRS-1, PI3K, AKT, GSK-3\u03b2. Real-time PCR was performed to assess mRNA expression of these targets in multiple tissues. This work is reported in accordance with the ARRIVE guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Following RYGB, body weight, fasting blood glucose, and HOMA-IR improved significantly. IGFBP-1 levels were significantly elevated post-surgery, along with marked upregulation of IRS-1, PI3K, and AKT, and downregulation of GSK-3\u03b2 in WT mice. These changes were absent in KO mice. Histomorphometric analysis demonstrated that RYGB reversed multi-organ pathological changes (cardiomyocyte hypertrophy, hepatic steatosis, glomerular enlargement, adipocyte hypertrophy) in WT mice but only partially in KO mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Metabolic surgery upregulates IGFBP-1 expression. Elevated IGFBP-1 is associated with upregulation of the IRS\/PI3K\/AKT\/GSK-3\u03b2 signaling axis and improved insulin sensitivity. IGFBP-1 is necessary for achieving complete normalization of glucose homeostasis and multi-tissue repair after RYGB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1859266","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:21:07Z","timestamp":1784175667000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["IGFBP-1 is associated with IRS signaling upregulation and contributes to metabolic recovery post-Roux-en-Y bypass"],"prefix":"10.3389","volume":"17","author":[{"given":"Tengfei","family":"Qi","sequence":"first","affiliation":[{"name":"Department of General Surgery, The General Hospital of Southern Theater Command","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The General Hospital of Southern Theater Command","place":["Guangzhou, China"]},{"name":"Department of Hepatobiliary Surgery and Liver Transplantation Center, General Hospital of Southern Theater Command","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangping","family":"Wu","sequence":"additional","affiliation":[{"name":"Jinshazhou Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jipei","family":"He","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The General Hospital of Southern Theater Command","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Research, General Hospital of Southern Theater Command","place":["Guangzhou, China"]},{"name":"Southern Medical University School of Laboratory Medicine and Biotechnology","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The General Hospital of Southern Theater Command","place":["Guangzhou, China"]},{"name":"The First School of Clinical Medicine, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00618-8","article-title":"Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants","volume":"387","year":"2016","journal-title":"Lancet (London, England)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199509000-00011","article-title":"Who would have thought it? 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