{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:38:34Z","timestamp":1791517114917,"version":"4.3.4"},"reference-count":72,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health\u2019s National Heart, Lung, and Blood Institute","award":["R01HL144146"],"award-info":[{"award-number":["R01HL144146"]}]},{"name":"National Institute of Health\u2019s National Heart, Lung, and Blood Institute","award":["R01HL168500"],"award-info":[{"award-number":["R01HL168500"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type-2 Diabetes Mellitus (T2DM) is related to cardiac arrhythmias. The stellate ganglion (SG), part of the sympathetic nervous system, regulates heart function. Within the SG, satellite glial cells (SGCs) have gap junction channels (Cx43). Increased Cx43 permeability induces SGC depolarization and activates the PKC-MAPK14-ADAM17 signaling pathway, releasing some endogenous factors that stimulate nearby cardiac postganglionic sympathetic neurons (CPSN). This study investigated the activation of the PKC-MAPK14-ADAM17 signaling pathway in T2DM SGs and SGCs as a novel mechanism of sympathetic overactivation. A total of 56 Sprague-Dawley rats were randomly assigned to sham and T2DM groups, and T2DM was induced using a high-fat diet combined with low-dose streptozotocin. Real-time RT-PCR, Western blot, and ELISA quantified mRNA\/protein expression and enzymatic activity. The patch clamp technique assessed neuronal voltage-gated Ca2+ currents and action potentials, while electrophysiological recording measured cardiac sympathetic nerve activity (CSNA). T2DM rats exhibited marked upregulation of MAPK14, PKC-\u03b1, and ADAM17 mRNA\/protein in the SG, alongside elevated enzymatic activities of PKC and ADAM17. T2DM also increased Ca2+ currents and neuronal excitability in the CPSN and induced the elevation of the CSNA. Upregulated PKC-MAPK-ADAM17 signaling in the SG might contribute to cardiac sympathetic overactivation in T2DM rats by enhancing the cell excitability of the CPSN.<\/jats:p>","DOI":"10.3390\/ijms27020723","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:13:01Z","timestamp":1768209181000},"page":"723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Impact of PKC-MAPK Signaling on Cardiac Sympathetic Overactivation in Type-2 Diabetes Mellitus"],"prefix":"10.3390","volume":"27","author":[{"given":"Jaswinder","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1130-4504","authenticated-orcid":false,"given":"Afia Saabea","family":"Owusu Konadu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Shabaltiy","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5407-2761","authenticated-orcid":false,"given":"Yu-Long","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"ref_1","unstructured":"Atlas, D. 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