{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T19:27:32Z","timestamp":1784921252111,"version":"3.55.0"},"reference-count":47,"publisher":"American Diabetes Association","issue":"12","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"vor","delay-in-days":289,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"DOI":"10.13039\/501100000082","name":"Cystic Fibrosis Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000082","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,12,1]]},"abstract":"<jats:p>Cystic fibrosis (CF) is the result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CF-related diabetes affects 50% of adult CF patients. How CFTR deficiency predisposes to diabetes is unknown. Herein, we examined the impact of the most frequent cftr mutation in humans, deletion of phenylalanine at position 508 (\u0394F508), on glucose homeostasis in mice. We compared \u0394F508 mutant mice with wild-type (WT) littermates. Twelve-week-old male \u0394F508 mutants had lower body weight, improved oral glucose tolerance, and a trend toward higher insulin tolerance. Glucose-induced insulin secretion was slightly diminished in \u0394F508 mutant islets, due to reduced insulin content, but \u0394F508 mutant islets were not more sensitive to proinflammatory cytokines than WT islets. Hyperglycemic clamps confirmed an increase in insulin sensitivity with normal \u03b2-cell function in 12- and 18-week-old \u0394F508 mutants. In contrast, 24-week-old \u0394F508 mutants exhibited insulin resistance and reduced \u03b2-cell function. \u03b2-Cell mass was unaffected at 11 weeks of age but was significantly lower in \u0394F508 mutants versus controls at 24 weeks. This was not associated with gross pancreatic pathology. We conclude that the \u0394F508 CFTR mutation does not lead to an intrinsic \u03b2-cell secretory defect but is associated with insulin resistance and a \u03b2-cell mass deficit in aging mutants.<\/jats:p>","DOI":"10.2337\/db14-0810","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T05:40:59Z","timestamp":1448430059000},"page":"4112-4122","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":36,"title":["The \u0394F508 Mutation in the Cystic Fibrosis Transmembrane Conductance Regulator Is Associated With Progressive Insulin Resistance and Decreased Functional \u03b2-Cell Mass in Mice"],"prefix":"10.2337","volume":"64","author":[{"given":"Ghislaine","family":"Font\u00e9s","sequence":"first","affiliation":[{"name":"Montreal Diabetes Research Center, University of Montreal, Quebec, Canada"},{"name":"University of Montreal Hospital Research Centre, University of Montreal, Montreal, Quebec, 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