Supplementary Figure 6: Proposed model for the physiological role of IL-1β and insulin in the regulation of glucose metabolism in response to food intake.

Food ingestion during feeding increases the number of peritoneal macrophages. These macrophages are stimulated by bacterial products and glucose to increase the production and release of IL-1β. Increased IL-1β concentrations will then enhance the continuous postprandial insulin secretion from pancreatic β cells via the highly expressed IL-1 receptor 1 (IL-1R1) and the IL-1 receptor-associated kinase-4 (IRAK4). The secreted insulin binds to its receptor (InsR) on macrophages, leading to enhanced glucose uptake through the glucose transporter GLUT1, AKT phosphorylation (pAKT) as well as hexokinase 2 (HK2) and glycolytic activity leading to ROS production. This further stimulates macrophage- derived pro-IL-1β-maturation by the NLRP3 inflammasome. Finally, increased levels of IL-1β and insulin stimulate glucose uptake into muscle, adipose tissue and immune cells that consequently decrease glycemia, thereby limiting the postprandial inflammatory response.