Nutrition-/diet-induced changes in gene expression in pancreatic ß-cells.

ABSTRACT

ß-Cell dysfunction is a critical component in the development of type 2 diabetes. Whilst both genetic and environmental factors contribute to the development of the disease, relatively little is known about the molecular network that is responsible for diet-induced functional changes in pancreatic ß-cells. Recent genome-wide association studies for diabetes-related traits have generated a large number of candidate genes that constitute possible links between dietary factors and the genetic susceptibility for ß-cell failure. Here, we summarize recent approaches for identifying nutritionally regulated transcripts in islets on a genome-wide scale. Polygenic mouse models for type 2 diabetes have been instrumental for investigating the mechanism of diet-induced ß-cell dysfunction. Enhanced oxidative metabolism, triggered by a combination of dietary carbohydrates and fat, appears to play a critical role in the pathophysiology of diet-induced impairment of islets. More systematic studies of gene-diet interactions in ß-cells of rodent models in combination with genetic profiling might reveal the regulatory circuits fundamental for the understanding of diet-induced impairments of ß-cell function in humans.