Characterizing the metabolic heterogeneity of pancreatic beta cells

The pancreatic β cells have a key role in maintaining glucose homeostasis by continually monitoring nutritional cues and secreting well-adjusted insulin levels. Obesity and insulin resistance lead to hyperglycemia and remain major risk factors for T2D; however, the ability of beta cells to increase their functional capacity compensates for the increasing demand for insulin and counteracts the development of T2D in most people.
Beta cell compensation is a key intervention process, but the function and mechanism are yet to be determined.

Although β cells are considered a homogeneous population that responds to glucose and other nutritional stimuli similarly, our functional experiments show otherwise. By detecting mTOR activity in single beta cells and measuring insulin secretion in response to nutrients, we demonstrate that subpopulations of β cells respond to nutrients differently. For example, we found a small beta cell subpopulation sensitive to amino acids, while most beta cells are not. Moreover, we find that the subpopulation of beta cells that responds to amino acids increases in pre-diabetic conditions.