Figure 2.

IRE1α exerts a broad range of tissue- or cell type-specific functions in metabolic organs. IRE1α responds to metabolic cues and nutrient stress signals, exerting broad and profound metabolic effects. In the hypothalamus, IRE1α is implicated in energy balance control and regulation of leptin sensitivity. In pancreatic islets, IRE1α responds to glucose stimulation and acts to control insulin biosynthesis, processing, and secretion, as well as the compensatory proliferation and growth of β-cells in the setting of metabolic ER stress and insulin resistance. In the liver, IRE1α responds to both anabolic and catabolic stimulatory signals and regulates a variety of metabolic pathways in glucose and lipid metabolism as indicated. In adipose tissues, IRE1α performs regulatory functions in adipogenesis, thermogenesis, and metabolic inflammation.