2022 Henry Pickering Bowditch Award Lecture: Nutrient Sensing in the Placenta and Pancreas: Fetal Programming of Obesity and Type 2 Diabetes

During pregnancy, hormonal and metabolic changes in the pregnant person facilitate proper fetal development and supply necessary nutrients to the fetus. However, aberrations of maternal metabolic alterations, such as obesity and gestational diabetes mellitus, can lead to permanent structural and functional changes in the developing fetal tissues, predisposing the offspring to metabolic diseases that manifest later in life. Pregnancy complications such as maternal obesity and gestational diabetes have long-term effects on fetal pancreatic beta cell mass and function that result in an increased risk of type 2 diabetes later in life.

One active area of physiological research is how the placenta integrates maternal signals with placental nutrient flux to the growing fetus. For example, pregnancy causes an increase in the parent’s insulin levels and insulin resistance, but insulin does not cross the placenta and is not thought to be a major mediator of placental glucose transfer. Instead, parental insulin acts on the placental insulin receptor and its downstream target nutrient-sensing protein mTOR kinase. Emilyn Alejandro, PhD, and her team recently reported that placental insulin receptor and mTORC1 signaling are important regulators of metabolic health trajectory of the offspring. They are investigating how direct manipulation of nutrient sensor proteins in insulin-producing cells can regulate functional beta cell mass and function.

In this webinar, Emilyn Alejandro will discuss how insulin and mTOR signaling in the placenta may influence fetal programming of metabolic health and the possible long-term outcomes in the offspring, especially when insulin is increased in obese gestational diabetes models. The purpose of this talk will illustrate how researchers have come to explore fetal programming of metabolic health by placental nutrient sensing as an exciting new way of thinking about the early-life factors that contribute to the development of type 2 diabetes.