Controlling Beta Cell Functionality via Nutrient-Sensing Mechanisms

How organs functionally adjust to changes in the nutritional environment is a critical question in physiology. At birth, mammals are faced with a challenge as they break from the supportive maternal environment into the outside world, a transition requiring independent physiology. Because nutrient consumption changes from relatively constant in utero to pulsatile after birth, the metabolic adaptation of the neonate to intermittent feeding and glucose fluctuations is critical. Pancreatic beta cell maturation, for example, involves developing a higher threshold for glucose-stimulated insulin secretion (GSIS), as evidenced by inhibition of insulin secretion at low glucose and enhanced insulin secretion in response to high glucose. The initial functional maturation period in which responsiveness to glucose is acquired occurs within the first week after birth. Beta cells continue to develop, however, and improve in secretory function after weaning.
Previously, I described a perinatal change in the regulation of mTORC1 signaling by nutrients that modifies the dynamics of insulin secretion after birth. These findings demonstrated a role for nutrient sensing by mTORC1 in the initiation of functional maturation of pancreatic beta cells (Helman, 2020).
In the lab, we are investigating the following topics: (1) Functional heterogeneity in nutrient-sensing (2) Metabolic adaptations to nutritional changes in development and adulthood (3) Stem cell differentiation: What can we learn from stem cell differentiation on the physiological importance of nutrients and nutrient-sensing mechanisms?
I will present how nutrient-sensing mechanisms lead to functional maturation and how nutrient-sensing heterogeneity affects the functionality of mature islets.