{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:34:43Z","timestamp":1790642083946,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":52,"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":["81771357"],"award-info":[{"award-number":["81771357"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Painful diabetic neuropathy (PDN) is a frequent and troublesome complication of diabetes, with little effective treatment. PDN is characterized by specific spinal microglia\u2010mediated neuroinflammation. Insulin\u2010like growth factor 1 (IGF\u20101) primarily derives from microglia in the brain and serves a vital role in averting the microglial transition into the proinflammatory M1 phenotype. Given that epigallocatechin\u20103\u2010gallate (EGCG) is a potent anti\u2010inflammatory agent that can regulate IGF\u20101 signaling, we speculated that EGCG administration might reduce spinal microglia\u2010related neuroinflammation and combat the development of PDN through IGF\u20101\/IGF1R signaling. <jats:italic>Methods<\/jats:italic>. Type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) in mice. The protein expression level of IGF\u20101, its receptor IGF1R, interleukin 1<jats:italic>\u03b2<\/jats:italic> (IL\u20101<jats:italic>\u03b2<\/jats:italic>), tumor necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> (TNF\u2010<jats:italic>\u03b1<\/jats:italic>), and inducible nitric oxide synthase (iNOS) was determined by Western blot or immunofluorescence. <jats:italic>Results<\/jats:italic>. The spinal IGF\u20101 expression markedly decreased along with the presence of pain\u2010like behaviors, the spinal genesis of neuroinflammation (increased IL\u20101<jats:italic>\u03b2<\/jats:italic>, TNF\u2010<jats:italic>\u03b1<\/jats:italic>, and Iba\u20101<jats:sup>+<\/jats:sup> microglia), and the intensified M1 microglia polarization (increased iNOS<jats:sup>+<\/jats:sup>Iba\u20101<jats:sup>+<\/jats:sup> microglia) in diabetic mice. IGF\u20101 could colocalize with neurons, astrocytes, and microglia, but only microglial IGF\u20101 was repressed in T1DM mice. Furthermore, we found that i.t. administration of mouse recombinant IGF\u20101 (rIGF\u20101) as well as i.t. or i.p. treatment with EGCG alleviated the diabetes\u2010induced pain\u2010like behaviors, reduced neuroinflammation (suppressed IL\u20101<jats:italic>\u03b2<\/jats:italic>, TNF\u2010<jats:italic>\u03b1<\/jats:italic>, and Iba\u20101<jats:sup>+<\/jats:sup> microglia), prevented the M1 microglia polarization (less iNOS<jats:sup>+<\/jats:sup>Iba\u20101<jats:sup>+<\/jats:sup> microglia), and restored the microglial IGF\u20101 expression. <jats:italic>Conclusions<\/jats:italic>. Our data highlighted the importance of maintaining spinal IGF\u20101 signaling in treating microglia\u2010related neuroinflammation in PDN. This study also provides novel insights into the neuroprotective mechanisms of EGCG against neuropathic pain and neuroinflammation through IGF\u20101 signaling, indicating that this agent may be a promising treatment for PDN in the clinical setting.<\/jats:p>","DOI":"10.1155\/2022\/6773662","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T21:20:13Z","timestamp":1645564813000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF\u20101 Signaling Which Can Be Rescued by Green Tea Polyphenol EGCG in 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