{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T02:07:32Z","timestamp":1772935652531,"version":"3.50.1"},"reference-count":38,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":2697,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:p>Mutations to the ATP-sensitive K+ channel (KATP channel) that reduce the sensitivity of ATP inhibition cause neonatal diabetes mellitus via suppression of \u03b2-cell glucose-stimulated free calcium activity ([Ca2+]i) and insulin secretion. Connexin-36 (Cx36) gap junctions also regulate islet electrical activity; upon knockout of Cx36, \u03b2-cells show [Ca2+]i elevations at basal glucose. We hypothesized that in the presence of overactive ATP-insensitive KATP channels, a reduction in Cx36 would allow elevations in glucose-stimulated [Ca2+]i and insulin secretion to improve glucose homeostasis. To test this, we introduced a genetic knockout of Cx36 into mice that express ATP-insensitive KATP channels and measured glucose homeostasis and islet metabolic, electrical, and insulin secretion responses. In the normal presence of Cx36, after expression of ATP-insensitive KATP channels, blood glucose levels rapidly rose to &amp;gt;500 mg\/dL. Islets from these mice showed reduced glucose-stimulated [Ca2+]i and no insulin secretion. In mice lacking Cx36 after expression of ATP-insensitive KATP channels, normal glucose levels were maintained. Islets from these mice had near-normal glucose-stimulated [Ca2+]i and insulin secretion. We therefore demonstrate a novel mechanism by which islet function can be recovered in a monogenic model of diabetes. A reduction of gap junction coupling allows sufficient glucose-stimulated [Ca2+]i and insulin secretion to prevent the emergence of diabetes.<\/jats:p>","DOI":"10.2337\/db13-1048","type":"journal-article","created":{"date-parts":[[2014,1,24]],"date-time":"2014-01-24T03:45:21Z","timestamp":1390535121000},"page":"1685-1697","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":22,"title":["Decreasing Cx36 Gap Junction Coupling Compensates for Overactive KATP Channels to Restore Insulin Secretion and Prevent Hyperglycemia in a Mouse Model of Neonatal Diabetes"],"prefix":"10.2337","volume":"63","author":[{"given":"Linda M.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of Colorado, Anschutz Medical Campus, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Pozzoli","sequence":"additional","affiliation":[{"name":"Department of 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