{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T15:06:05Z","timestamp":1776956765469,"version":"3.51.4"},"reference-count":58,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T00:00:00Z","timestamp":1562803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000201","name":"Lawson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000201","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Pancreatic \u03b2\u2010cell dysfunction is hypothesized to be the significant determinant of gestational diabetes pathogenesis, however pancreatic samples from patients are scarce.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study reports a novel mouse model of gestational glucose intolerance in pregnancy, originating from previous nutrition restriction <jats:italic>in utero<\/jats:italic>, in which glucose intolerance was restricted to late gestation as is seen in human gestational diabetes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Glucose intolerance was attributed to reduced \u03b2\u2010cell proliferation, leading to impaired gestational \u03b2\u2010cell mass expansion in maternal endocrine pancreas, in addition to reduced glucose\u2010stimulated insulin secretion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This model reproduces some of the features of gestational diabetes and is suitable for testing safe therapeutic interventions that increase \u03b2\u2010cell mass during pregnancy and prevent or reverse gestational glucose intolerance.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Gestational diabetes mellitus (GDM) is an increasingly prevalent form of diabetes that appears during pregnancy. Pathological studies link a failure to adaptively increase maternal pancreatic \u03b2\u2010cell mass (BCM) in pregnancy to GDM. Due to the scarcity of pancreatic samples from GDM patients, we sought to develop a novel mouse model for impaired gestational glucose tolerance. Mature female C57Bl\/6 mouse offspring (F1) born to dams fed either a control (C) or low\u2010protein (LP) diet during gestation and lactation were randomly allocated into two subsequent study groups: pregnant (CP, LPP) or non\u2010pregnant (CNP, LPNP). Glucose tolerance tests were performed at gestational day (GD) 9, 12 and 18. Subsequently, pancreata were removed for fluorescence immunohistochemistry to assess \u03b1\u2010cell mass (ACM), BCM and \u03b2\u2010cell proliferation. An additional group of animals was used to measure insulin secretion from isolated islets at GD18. LPP females displayed glucose intolerance compared to CP females at GD18 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). BCM increased threefold at GD18 in CP females. However, LPP females had reduced BCM expansion (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) concurrent with reduced \u03b2\u2010cell proliferation at GD12 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). LPP females also had reduced ACM expansion at GD18 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). LPP islets had impaired glucose\u2010stimulated insulin secretion <jats:italic>in vitro<\/jats:italic> compared to CP islets (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Therefore, impaired glucose tolerance during pregnancy is associated with a failure to adequately adapt BCM, as a result of reduced \u03b2\u2010cell proliferation, in addition to lower glucose\u2010stimulated insulin secretion. This model could be used to evaluate novel interventions during pregnancy to increase BCM or function as a strategy to prevent\/reverse GDM.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp277884","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T16:16:46Z","timestamp":1560788206000},"page":"4237-4250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A mouse model of gestational glucose intolerance through exposure to a low protein diet during fetal and neonatal development"],"prefix":"10.1113","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2698-7224","authenticated-orcid":false,"given":"Sandra K.","family":"Szlapinski","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  1151 Richmond St. London ON Canada"},{"name":"Lawson Health Research Institute St Joseph's Health Care  268 Grosvenor St. F4\u2010124 London ON 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