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

Abstract

The deleterious effect of chronic activation of the IL-1 system on type 2 diabetes and other metabolic diseases is well documented. However, a possible physiological role for IL-1 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, in a glucose-dependent manner. Subsequently, IL-1 contributed to the postprandial stimulation of insulin secretion. Accordingly, lack of endogenous IL-1 signaling in mice during refeeding and obesity diminished the concentration of insulin in plasma. IL-1 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 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 and insulin in the regulation of both metabolism and immunity. 30reactive oxygen species production, and NLRP3 inflammasome-mediated IL-1β secretion. 31Post-prandial inflammation is limited by normalization of glycemia and can be prevented by 32 inhibition of sodium-glucose cotransporter 2 (SGLT2). Our findings identify a physiological 33 role for IL-1β and insulin in the regulation of both metabolism and immunity.

Insulin Modulates Cytokine Release, Collagen and Mucus Secretion in Lung Remodeling of Allergic Diabetic Mice

“…Moreover, the synergistic contribution of insulin and proinflammatory cytokines to the stimulation of the immune system has been reported. Dror et al (34) found that insulin stimulates IL-1b secretion by resident macrophages, which could explain the mechanisms by which insulin restored IL-1β levels in our study.…”

Weight loss independent changes in adipose tissue macrophage and T cell populations after sleeve gastrectomy in mice

“…Whether this is relevant to the metabolic improvements observed after surgery is unclear, yet it indicates that the immune environment is significantly altered with VSG which fits with the potent upregulation of T cells present in the eWAT. Recently, there has also been evidence that some cytokines can act directly on systemic metabolic changes via immune cells, such as IL-1β being produced by peritoneal macrophages in response to feeding and subsequently acting on the pancreatic β cells to increase insulin secretion [36]. In the light of this, there is even more reason to believe that changes in the immune cells/cytokines after surgery could be relevant to metabolic improvements after surgery.…”

Changes in Host Immune–Endocrine Relationships during Tuberculosis Treatment in Patients with Cured and Failed Treatment Outcomes

“…This study, however, has several limitations such as the small sample sizes and the fact that dietary intake and blood collection time was not standardized. Not only hormone but also cytokine concentrations, for instance, IL-1β are known to change post-prandially (20), yet this is almost never considered in TB biomarker studies available in the literature and should be taken into account in any future studies. Despite the limitations, typical treatment responses were observed when looking at the changes in hormone concentrations during TB treatment and it would appear that cortisol, DHEA, T4, and amylin (total) are the major role players in the host response to M.tb and are potential marker candidates to differentiate treatment outcome.…”