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Pancreatic islet serotonin signaling plays an important role in \u03b2-cell proliferation in pregnancy, and environmental and genetic factors that disrupt serotonin signaling are associated with gestational diabetes in mice. Our previous studies show that pregnant C57BL\/6J mice fed a diet that is low in vitamin B6, a critical co-factor in serotonin synthesis, develop hyperglycemia and glucose intolerance, phenotypes that are consistent with gestational diabetes in humans. The current study shows that, unlike in the C57BL\/6J mice, low vitamin B6 diet does not alter glucose tolerance and insulin secretion in pregnant DBA\/2J mice. The hypothesis to be tested in the current study is that pregnant DBA\/2J mice are protected against low vitamin B6\u2013induced gestational diabetes due to their higher expression and enzymatic activities of tissue nonspecific alkaline phosphatase (ALPL) relative to C57BL\/6J. ALPL is a rate-limiting enzyme that regulates vitamin B6 bioavailability. Interestingly, treating pregnant DBA\/2J mice with 7.5\u2005mg\/kg\/day of the ALPL inhibitor SBI-425 is associated with glucose intolerance in low vitamin B6\u2013fed mice, implying that inhibition of ALPL activity is sufficient to modulate resilience to low vitamin B6\u2013induced metabolic impairment.<\/jats:p>","DOI":"10.1210\/endocr\/bqad130","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T16:51:56Z","timestamp":1692982316000},"source":"Crossref","is-referenced-by-count":8,"title":["Susceptibility to Low Vitamin B6 Diet\u2013induced Gestational Diabetes Is Modulated by Strain Differences in Mice"],"prefix":"10.1210","volume":"164","author":[{"given":"Philip","family":"Spinelli","sequence":"first","affiliation":[{"name":"Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley 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