Postprandial macrophage-derived IL-1β stimulates insulin, and both synergistically promote glucose disposal and inflammation

The deleterious effect of chronic activation of the 1L-1 beta system on type 2 diabetes and other metabolic diseases is well documented. However, a possible physiological role for IL-1 beta in glucose metabolism has remained unexplored. Here we found that feeding induced a physiological increase in the number of peritoneal macrophages that secreted IL-1 beta, in a glucose dependent manner. Subsequently, IL-1 beta contributed to the postprandial stimulation of insulin secretion. Accordingly, lack of endogenous IL-1 beta signaling in mice during refeeding and obesity diminished the concentration of insulin in plasma. IL-1 beta and insulin increased the uptake of glucose into macrophages, and insulin reinforced a pro-inflammatory pattern via the insulin receptor, glucose metabolism, production of reactive oxygen species, and secretion of IL-1 beta mediated by the NLRP3 inflammasome. Postprandial inflammation might be limited by normalization of glycemia, since it was prevented by inhibition of the sodium glucose cotransporter SGLT2. Our findings identify a physiological role for IL-1 beta and insulin in the regulation of both metabolism and immunity.