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

Dror et al. Nat Immunol (2017) 18: 283-292.

Speaker: Meng-Shan Tsai (蔡孟珊)                                             Time: 13:10~14:00, Jun. 21, 2017

Commentator: Dr. Guey-Chuen Perng (彭貴春 老師)                Place: Room 601

Abstract:

Interleukin 1β (IL-1β) is a central mediator between the immune system and metabolic pathways, a concept known as immunometabolism [1]. The increased production of circulating IL-1β has been emerged as a hallmark of chronic, low-grade inflammation with the obvious metabolic connection, correlated with not only obesity but also associated with several clinical diseases such as osteoarthritis, cardiovascular disease, and type 2 diabetes [2]. Janus functions of IL-1β has been elucidated that at a low concentration and a limited period exposure exerts the beneficial effect on islet β-cells being responsible for insulin secretion, while the opposite consequent of β-cells is following the longer exposure time with a high concentration, which promotes inflammation and metabolic dysregulation [3]. However, the physiological effect of IL-1β on glucose metabolism remains unexplored. To investigate the postprandial regulation of IL-1β on metabolic influence, the authors perform studies on various mouse models and of cells. Overnight fasting followed by refeeding increases the circulating level of IL-1β induced from the source of peritoneal macrophages and the secretion of insulin both in vivo and ex vivo. Macrophages are confirmed as the source of IL-1β which is not increased in mice that lack of IL-1β in circulation, of IL-1β in the myeloid lineage, or of type 1 IL-1 receptor during refeeding. Next, the authors verify the elevated level of IL-1β promotes insulin secretion and glucose tolerance via depleting macrophages or injecting recombinant IL-1β in mice. Finally, they determine the role of insulin on immune cells. Insulin induces the secretion of IL-1β from M1 macrophages and regulates the glucose disposal together with IL-1β. In addition, improving the excretion or blocking the absorption of glucose limits the levels of glycaemia, insulin, and IL-1β. Collectively, IL-1β and insulin synergistically promote each other to increase the consumption of glucose in macrophages after food intake and deliver the sweet link between immunology and metabolism. Moreover, this investigation might give the suggestion for the therapeutic strategy in metabolic diseases.

References:

1.    Mathis D. et al. Immunometabolism: an emerging frontier. Nat. Rev. Immunol. (2011) 11:81

2.    Dinarello, C.A. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood (2011) 117: 3720-3732

3.    Donath, M.Y. et al. Cytokine production by islets in health and diabetes: cellular origin, regulation and function. Trends. Endocrinol. Metab. (2010) 21: 261-267