{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T22:10:54Z","timestamp":1777759854607,"version":"3.51.4"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,22]],"date-time":"2025-06-22T00:00:00Z","timestamp":1750550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,6,22]],"date-time":"2025-06-22T00:00:00Z","timestamp":1750550400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic gastrointestinal dysfunction is a common complication of long\u2010standing diabetes and poorly controlled hyperglycemia, often associated with considerable morbidity. However, the cellular mechanisms that underlie the diabetic impairment of the intestine remain poorly understood. In the present study, we examined whether alterations in myenteric neuron excitability contribute to diabetic intestinal dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Type 2 diabetic mice were generated by administering a cafeteria diet for 21\u2009weeks and an intraperitoneal injection of streptozotocin. Fasting blood glucose assessment and glucose and insulin tolerance tests confirmed the development of diabetes. The effect of diabetes on gut contractility was tested in an isolated organ bath, and patch\u2010clamp recordings were conducted to measure neuronal biophysical properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Type 2 diabetic mouse colons had a decreased twitch force amplitude and a decrease in the frequency of rhythmic spontaneous contractions. Moreover, S\u2010myenteric neurons of type 2 diabetic mice exhibited reduced excitability with a significant increase of 41% in rheobase. Incubation of na\u00efve myenteric neurons with colonic supernatants from type 2 diabetic mice recapitulated the effects on rheobase. Finally, the total voltage\u2010gated sodium currents were significantly decreased in myenteric neurons incubated with diabetic colonic supernatants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Inferences<\/jats:title>\n                    <jats:p>The decreased excitability and downregulation of total voltage\u2010gated sodium currents in the myenteric neurons of type 2 diabetic mice could partially explain the cellular mechanisms underlying the colonic dysmotility observed in patients with diabetes. Targeting voltage\u2010gated sodium channels may represent a novel therapeutic approach for modulating diabetic intestinal dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70105","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:39:17Z","timestamp":1750639157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decreased Excitability and Voltage\u2010Gated Sodium Currents in Myenteric Neurons Contribute to the Impairment of Gut Contraction in Type 2 Diabetes Mice"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2770-8197","authenticated-orcid":false,"given":"Guillermo A.","family":"Cabral\u2010Garc\u00eda","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda Centro de Ciencias B\u00e1sicas, Universidad Aut\u00f3noma de Aguascalientes  Aguascalientes 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