摘要

"Nutrigenomics" refers to the ability of nutrients to alter gene expression. Insulin secreting B-cells exhibit genomic and molecular changes that enhance their function when acutely exposed to physiological concentrations of glucose and fatty acids. However, chronic exposure, such as occurs in the hyperlipidemic, hyperglycemic state of obesity/prediabetes can exert deleterious effects on beta-cell function through alteration of gene expression. The genomic underpinnings of so-called glucolipotoxicity on the beta-cell and its relationship to development of type 2 diabetes will be discussed in this review article. For example, free fatty acids influence beta-cell gene expression by direct interaction with transcription factors such as peroxisome pro liferator-activated receptors. Glucose responsive genes include the insulin gene as well as genes involved in beta-cell survival and other functions. In addition, obesity is now recognized as a condition of chronic, low-level inflammation. The adipose tissue secretes multiple circulating hormones termed adipokines, and the relationship between these and the beta-cell has been termed adipotoxicity. The influence of adipokines on regulation of insulin secretion and beta-cell survival will be reviewed.

  • 出版日期2007-3