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Factors that reduce serotonin synthesis and perturb HTR2B signaling are associated with decreased \u03b2-cell number, impaired insulin secretion, and gestational glucose intolerance in mice. Albeit the tryptophan-serotonin pathway is dependent on vitamin B6 bioavailability, how vitamin B6 deficiency impacts \u03b2-cell proliferation during pregnancy has not been investigated. In this study, we created a vitamin B6 deficient mouse model and investigated how gestational deficiency influences maternal glucose tolerance. Our studies show that gestational vitamin B6 deficiency decreases serotonin levels in maternal pancreatic islets and reduces \u03b2-cell proliferation in an HTR2B-dependent manner. These changes were associated with glucose intolerance and insulin resistance, however insulin secretion remained intact. Our findings suggest that vitamin B6 deficiency-induced gestational glucose intolerance involves additional mechanisms that are complex and insulin independent.<\/jats:p>","DOI":"10.1038\/s42003-021-01900-0","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T07:03:37Z","timestamp":1616742217000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Vitamin B6 deficiency disrupts serotonin signaling in pancreatic islets and induces gestational diabetes in mice"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-7623","authenticated-orcid":false,"given":"Ashley M.","family":"Fields","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Welle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9111-7973","authenticated-orcid":false,"given":"Elaine S.","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clementina","family":"Mesaros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6480-2000","authenticated-orcid":false,"given":"Martha","family":"Susiarjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"1900_CR1","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.2337\/db15-1527","volume":"65","author":"RR Banerjee","year":"2016","unstructured":"Banerjee, R. 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