{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:12:23Z","timestamp":1779192743268,"version":"3.51.4"},"reference-count":0,"publisher":"S. Karger AG","issue":"1-2","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Physiol Biochem"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>Background\/Aims: The goal of this study was to determine the effect of dietary genistein (naturally occurring phytoestrogen) on jejunal secretory function in a clinically relevant model of diabetes and obesity, the leptin-defIcient ob\/ob mouse. Methods: We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from 12-week old male and female ob\/ob and lean C57Bl\/6J mice fed a genistein diet (600 mg genistein\/kg diet) for 4-weeks. Separate segments of jejunum were frozen for western blot determination of key proteins involved in secretory transport. Results: Basal Isc was signifIcantly decreased (by 33%, P&lt;0.05) in ob\/ob females versus leans, and genistein-diet reversed this. Similarly, in males, basal Isc was decreased (by 47%, P&lt;0.05) in ob\/ob mice versus leans, and genistein-diet reversed this. Inhibition with either clotrimazole (100 \u00b5M, bilateral) or ouabain (100 \u00b5M, basolateral) was signifIcantly reduced in ob\/ob mice compared to leans (P&lt;0.05), and genistein-diet reversed clotrimazole-sensitive inhibition in ob\/ob females, and reversed the ouabain-sensitive inhibition in males (indicating sex-dependent mechanisms). Our data suggested that PDE3 levels were dysregulated in ob\/ob females and genistein reversed this. Expression of total CFTR (normalized to actin) was signifIcantly decreased \u223c80% (P&lt;0.05) in all ob\/ob mice compared to leans, and genistein-diet was without effect. Expression of total NKCC1 (normalized to actin) was signifIcantly decreased \u223c80% (P&lt;0.05) in ob\/ob male mice versus leans, and genistein-diet reversed this. Conclusions: Our data suggests that the reduced basal jejunal Isc in ob\/ob female mice is a consequence of reduced CFTR expression, decreased activities of the basolateral KCa channel and Na+\/K+-ATPase, and in male mice reduced basal jejunal Isc is a consequence of reduced CFTR and NKCC1 expression, along with decreased activities of the basolateral KCa channel and Na+\/K+-ATPase. Genistein-diet has beneficial effects on basal Isc mediated by sex-dependent mechanisms in diabetic mice: in females via increased KCa-sensitive Isc and in males via increased Na+\/K+-ATPase activity and increased NKCC1 expression. Improved understanding of intestinal dysfunctions in the ob\/ob jejunum, may allow for the development of novel drug targets to treat obesity and diabetes, and may also be of benefit in CF-related diabetes.<\/jats:p>","DOI":"10.1159\/000452549","type":"journal-article","created":{"date-parts":[[2016,11,18]],"date-time":"2016-11-18T22:01:38Z","timestamp":1479506498000},"page":"335-346","source":"Crossref","is-referenced-by-count":10,"title":["Dietary Genistein Rescues Reduced Basal Chloride Secretion in Diabetic Jejunum via Sex-Dependent Mechanisms"],"prefix":"10.1159","volume":"40","author":[{"given":"Shawn","family":"Catmull","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faisal","family":"Masood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sydney","family":"Schacht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Dolan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Stegman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lana","family":"Leung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Layla","family":"Al-Nakkash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2016,11,21]]},"container-title":["Cellular Physiology and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/452549","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/452549","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/452549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:23:03Z","timestamp":1745428983000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000452549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016]]},"references-count":0,"journal-issue":{"issue":"1-2","published-online":{"date-parts":[[2016,11,18]]}},"URL":"https:\/\/doi.org\/10.1159\/000452549","archive":["Portico"],"relation":{},"ISSN":["1015-8987","1421-9778"],"issn-type":[{"value":"1015-8987","type":"print"},{"value":"1421-9778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016]]}}}