Pregnancy-induced changes in β-cell function: what are the key players?

Maternal metabolic adaptations during pregnancy ensure appropriate nutrient supply to the developing fetus. This is facilitated by reductions in maternal peripheral insulin sensitivity, which enables glucose to be available in the maternal circulation for transfer to the fetus for growth. To balance this process and avoid excessive hyperglycaemia and glucose intolerance in the mother during pregnancy, maternal pancreatic β-cells undergo remarkable changes in their function including increasing their proliferation and glucose-stimulated insulin secretion. In this review we examine how placental and maternal hormones work cooperatively to activate several signalling pathways, transcription factors and epigenetic regulators to drive adaptations in β-cell function during pregnancy. We also explore how adverse maternal environmental conditions, including malnutrition, obesity, circadian rhythm disruption and environmental pollutants, may impact the endocrine and molecular mechanisms controlling β-cell adaptations during pregnancy. The available data from human and experimental animal studies highlight the need to better understand how maternal β-cells integrate the various environmental, metabolic and endocrine cues and thereby determine appropriate β-cell adaptation during gestation. In doing so, these studies may identify targetable pathways that could be used to prevent not only the development of pregnancy complications like gestational diabetes that impact maternal and fetal wellbeing, but also more generally the pathogenesis of other metabolic conditions like type 2 diabetes.