Susceptibility to low vitamin B6 diet-induced gestational diabetes is modulated by strain differences in mice.

Gestational diabetes is a common pregnancy complication that adversely influences the health and survival of mother and child. Pancreatic islet serotonin signaling plays an important role in β-cell proliferation in pregnancy, and environmental and genetic factors that disrupts serotonin signaling are associated with gestational diabetes in mice. Our previous studies show that pregnant C57BL/6J mice fed 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 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 to low vitamin B6-induced gestational diabetes due to higher expression and enzymatic activities of tissue non specific 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 mg/kg/day of the ALPL inhibitor SBI-425 is associated with glucose intolerance in low vitamin B6-fed mice, implying that inhibition of ALPL activity is sufficient to modulate resilience to low vitamin B6-induced metabolic impairment.