{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:17:50Z","timestamp":1790727470531,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Besides its insulinotropic actions on pancreatic \u03b2 cells, neuroprotective activities of glucagon-like peptide-1 (GLP-1) have attracted attention. The efficacy of a GLP-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) for functional repair after sciatic nerve injury and amelioration of diabetic peripheral neuropathy (DPN) has been reported; however, the underlying mechanisms remain unclear. In this study, the bioactivities of Ex-4 on immortalized adult rat Schwann cells IFRS1 and adult rat dorsal root ganglion (DRG) neuron\u2013IFRS1 co-culture system were investigated. Localization of GLP-1R in both DRG neurons and IFRS1 cells were confirmed using knockout-validated monoclonal Mab7F38 antibody. Treatment with 100 nM Ex-4 significantly enhanced survival\/proliferation and migration of IFRS1 cells, as well as stimulated the movement of IFRS1 cells toward neurites emerging from DRG neuron cell bodies in the co-culture with the upregulation of myelin protein 22 and myelin protein zero. Because Ex-4 induced phosphorylation of serine\/threonine-specific protein kinase AKT in these cells and its effects on DRG neurons and IFRS1 cells were attenuated by phosphatidyl inositol-3\u2032-phosphate-kinase (PI3K) inhibitor LY294002, Ex-4 might act on both cells to activate PI3K\/AKT signaling pathway, thereby promoting myelination in the co-culture. These findings imply the potential efficacy of Ex-4 toward DPN and other peripheral nerve lesions.<\/jats:p>","DOI":"10.3390\/ijms22062971","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T11:38:58Z","timestamp":1615808338000},"page":"2971","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Exendin-4 Promotes Schwann Cell Survival\/Migration and Myelination In Vitro"],"prefix":"10.3390","volume":"22","author":[{"given":"Shizuka","family":"Takaku","sequence":"first","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Niimi","sequence":"additional","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2632-8488","authenticated-orcid":false,"given":"Hideji","family":"Yako","sequence":"additional","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9750-9596","authenticated-orcid":false,"given":"Kazunori","family":"Sango","sequence":"additional","affiliation":[{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.cmet.2013.04.008","article-title":"Pharmacology, Physiology, and Mechanisms of Incretin Hormone Action","volume":"17","author":"Campbell","year":"2013","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/dom.12849","article-title":"Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis","volume":"19","author":"Htike","year":"2017","journal-title":"Diabetes Obes. 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