Nutrigenetics and nutrigenomics insights into diabetes etiopathogenesis

Abstract

Diabetes mellitus (DM) is considered a global pandemic, and the incidence of DM continues to grow worldwide. Nutrients and dietary patterns are central issues in the prevention, development and treatment of this disease. The pathogenesis of DM is not completely understood, but nutrient-gene interactions at different levels, genetic predisposition and dietary factors appear to be involved. Nutritional genomics studies generally focus on dietary patterns according to genetic variations, the role of gene-nutrient interactions, gene-diet-phenotype interactions and epigenetic modifications caused by nutrients; these studies will facilitate an understanding of the early molecular events that occur in DM and will contribute to the identification of better biomarkers and diagnostics tools. In particular, this approach will help to develop tailored diets that maximize the use of nutrients and other functional ingredients present in food, which will aid in the prevention and delay of DM and its complications. This review discusses the current state of nutrigenetics, nutrigenomics and epigenomics research on DM. Here, we provide an overview of the role of gene variants and nutrient interactions, the importance of nutrients and dietary patterns on gene expression, how epigenetic changes and micro RNAs (miRNAs) can alter cellular signaling in response to nutrients and the dietary interventions that may help to prevent the onset of DM.

Figure 1

Nutrient-gene expression mechanisms. Nutrients present in food and diet can affect gene expression in a number of ways. They may directly act as ligands for transcription factors and change gene expression. Nutrients may be metabolized by different pathways, thereby modifying the concentration of substrates or intermediates that affect gene expression. Alternatively, the substrates or intermediates may act on or alter cell signaling pathways involved in gene expression. Moreover, nutrients may directly alter signal transduction pathways responsible for modifications in gene expression. Finally, the modifications in the signaling pathways, caused by nutrients, may modulate the metabolism of nutrients affecting gene expression. The modifications in gene expression may affect muscle, liver, pancreatic β cells, hypothalamus and adipose tissue, thereby regulating glucose homeostasis. The effects of these nutrient-gene interactions can be deleterious increasing DM risk and illness progression and complications or protective doing the opposite effects.

Figure 2

Effects of nutrients on β cell gene expression. Pancreatic β cells are able to sense dietary nutrients and respond to them releasing insulin. Different nutrients and their metabolites affect transcription of genes very important for maintenance of β cell function and integrity. Flavonoids upregulate the expression of genes involved in insulin synthesis, nutrient-induced insulin release and β cell proliferation and downregulate genes implicated in β cell apoptosis. Proteins positively regulate insulin synthesis, insulin release, β cell proliferation and growth upregulating the expression of mTOR, calcineurin and Pdx1. Fats upregulate OXPHOS genes leading to the generation of metabolic coupling factors critical for insulin exocytosis. On the other hand, a chronic exposure of β-cells to high levels of fats (mainly saturated fatty acids) induces excessive levels of ROS and pro-inflammatory cytokines, leading to an increased apoptosis. The upregulation of the expression of cytokine genes and genes involved in pro-inflammatory signaling pathways, together with the downregulation of genes implicated in the antioxidant defenses of β cells, contribute to β cell apoptosis. Moreover, chronic exposure to fats and their byproducts downregulate the expression of genes necessary for insulin synthesis, nutrient-induced insulin release, β cell integrity, maintenance and survival (Pdx1 and MafA). Impairment of β-cell function is a hallmark of pancreatic β-cell failure and may lead to development of DM.