{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T04:37:08Z","timestamp":1761712628925,"version":"build-2065373602"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T00:00:00Z","timestamp":1518393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>\n                    Diabetic neuropathy is the most common complication of diabetes and is frequently associated with foot ischemia and infection, but its pathogenesis is controversial. We hypothesized that proinsulin expression in peripheral blood mononuclear cells is a process relevant to this condition and could represent a link among hyperglycemia, nerve susceptibility, and diabetic foot lesions. We assessed proinsulin expression by using flow cytometry in dendritic cells from control participants and patients with type 2 diabetes with or without peripheral neuropathy or accompanied by diabetic foot. Among 32 non\u2010neuropathic and 120 neuropathic patients with type 2 diabetes, we performed leg electromyography and found average sensory sural nerve conduction velocities of 48 \u00b1 4 and 30 \u00b1 4 m\/s, respectively (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.03). Of those with neuropathy, 42 were without lesions, 39 had foot lesions, and 39 had neuroischemic foot lesions (allux oximetry &lt;30 mmHg). In this well\u2010defined diabetic population, but not in non\u2010diabetic participants, a progressively increasing level of peripheral blood dendritic cell proinsulin expression was detected, which directly correlated with circulating TNF\u2010\u03b1 levels (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.002) and multiple conduction velocities of leg nerves (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). These results are consistent with the hypothesis that, in type 2 diabetes, proinsulin\u2010expressing blood cells, possibly\n                    <jats:italic>via<\/jats:italic>\n                    their involvement in innate immunity, may play a role in diabetic peripheral neuropathy and foot lesions.\u2014Sambataro, M., Sambado, L., Trevisiol, E., Cacciatore, M., Furlan, A., Stefani, P. M., Seganfreddo, E., Durante, E., Conte, S., Della Bella, S., Paccagnella, A., dei Tos, A. P. Proinsulin\u2010expressing dendritic cells in type 2 neuropathic diabetic patients with and without foot lesions. FASEB J. 32, 3742\u20133751 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701279rr","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T16:43:42Z","timestamp":1518453822000},"page":"3742-3751","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Proinsulin\u2010expressing dendritic cells in type 2 neuropathic diabetic patients with and without foot lesions"],"prefix":"10.1096","volume":"32","author":[{"given":"Maria","family":"Sambataro","sequence":"first","affiliation":[{"name":"Endocrine, Metabolism, and Nutrition Disease Unit Department of Pathology Hematology Unit Immunohematology and Transfusional Medicine Service Neurology Unit Santa Maria di Ca\u2019 Foncello Hospital Treviso 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Transfusional Medicine Service Neurology Unit Santa Maria di Ca\u2019 Foncello Hospital Treviso Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Conte","sequence":"additional","affiliation":[{"name":"Neurology Unit Santa Maria di Ca\u2019 Foncello Hospital Treviso Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia Della","family":"Bella","sequence":"additional","affiliation":[{"name":"Department of Biomedical Technologies and Translational Medicine University of Milan Milan Italy"},{"name":"Laboratory of Clinical and Experimental Immunology Humanitas Clinical and Research Center Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agostino","family":"Paccagnella","sequence":"additional","affiliation":[{"name":"Endocrine, Metabolism, and Nutrition Disease Unit Department of Pathology Hematology Unit Immunohematology and Transfusional Medicine Service Neurology Unit Santa Maria di Ca\u2019 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