{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:45:32Z","timestamp":1782233132763,"version":"3.54.5"},"reference-count":235,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012550","name":"National Research, Development and Innovation Fund","doi-asserted-by":"crossref","award":["K135457"],"award-info":[{"award-number":["K135457"]}],"id":[{"id":"10.13039\/501100012550","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Brain Research Program NAP3","award":["HUN-REN TKI14016"],"award-info":[{"award-number":["HUN-REN TKI14016"]}]},{"name":"National Brain Research Program NAP3","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}]},{"name":"sponsorship of the Hungarian Ministry of Culture and Innovation"},{"name":"Stipendium Hungaricum and China Scholarship Council"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide exerting, among others, strong trophic and protective effects. It plays a role in several physiological functions, including glucose homeostasis. The protective effects of PACAP are mainly mediated via its specific PAC1 receptor by stimulating anti-inflammatory, anti-apoptotic and antioxidant pathways. The aim of the present review is to summarize data on the protective effects of PACAP in the three major complications of diabetes, retinopathy, nephropathy and neuropathy, as well as some other complications. In type 1 and type 2 diabetic retinopathy models and in glucose-exposed cells of the eye, PACAP counteracted the degeneration of retinal layers and inhibited apoptosis and factors leading to abnormal vessel growth. In models of nephropathy, kidney morphology was better retained after PACAP administration, with decreased apoptosis and fibrosis. In diabetic neuropathy, PACAP protected against axonal\u2013myelin lesions and less activation in pain processing centers. This neuropeptide has several other beneficial effects in diabetes-induced complications like altered vascular response, cognitive deficits and atherosclerosis. The promising therapeutic effects of PACAP in several pathological conditions have encouraged researchers to design PACAP-related drugs and to develop ways to enhance tissue delivery. These intentions are expected to result in overcoming the hurdles preventing PACAP from being introduced into therapeutic treatments, including diabetes-related conditions.<\/jats:p>","DOI":"10.3390\/ijms26199650","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T07:57:27Z","timestamp":1759478247000},"page":"9650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Protective Effects of PACAP in Diabetic Complications: Retinopathy, Nephropathy and Neuropathy"],"prefix":"10.3390","volume":"26","author":[{"given":"Dora","family":"Reglodi","sequence":"first","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Tamas","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inez","family":"Bosnyak","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8112-8633","authenticated-orcid":false,"given":"Tamas","family":"Atlasz","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"},{"name":"Department of Sports Biology and Kinesiology, Faculty of Sciences, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edina","family":"Szabo","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Li","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Horvath","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balazs","family":"Opper","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kiss","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Lucas","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0173-4885","authenticated-orcid":false,"given":"Grazia","family":"Maugeri","sequence":"additional","affiliation":[{"name":"Section of Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata Grazia","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1114-8265","authenticated-orcid":false,"given":"Velia","family":"D\u2019Agata","sequence":"additional","affiliation":[{"name":"Section of Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Fabian","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyongyver","family":"Reman","sequence":"additional","affiliation":[{"name":"HUN REN-PTE PACAP Research Group, Department of Anatomy, University of Pecs Medical School, 7624 Pecs, 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