Impact of the exposome on the development and function of pancreatic ?-cells

The development and plasticity of the endocrine pancreas responds to both the intrauterine and postnatal exposome in a constant attempt to predict and respond to alterations in nutritional availability and metabolic requirements. Both under-and over-nutrition in utero, or exposure to adverse environmental pollutants or maternal behaviors, can each lead to altered 13-cell or function at birth, and a subsequent mismatch in pancreatic hormonal demands and secretory capacity postnatally. This can be further exacerbated by metabolic stress postnatally such as from obesity or pregnancy, resulting in an increased risk of gestational diabetes, type 2 diabetes, and even type 1 diabetes. This review will discuss evidence identifying the cellular pathways in early life whereby the plasticity of the endocrine pancreatic can become pathologically limited. By necessity, much of this evidence has been gained from animal models, although extrapolation to human fetal development is possible from the fetal growth trajectory and study of the newborn. Cellular limitations to plasticity include the balance between 13-cell proliferation and apoptosis, the appearance of 13-cell oxidative stress, impaired glucose stimulated insulin secretion, and sensitivity to circulating cytokines and responsiveness to programmed death receptor-1. Evidence suggests that many of the cellular pathways responsible for limiting 13-cell plasticity are related to paracrine interactions within the islets of Langerhans.

Automated summary

The development and plasticity of the endocrine pancreas are influenced by both intrauterine and postnatal factors. Perturbations in nutritional availability and metabolic requirements can lead to altered pancreatic function and increased risk of diabetes. Cellular pathways within the pancreas, especially paracrine interactions, play a crucial role in limiting the plasticity of insulin-producing cells.