Complement at the crossroads of inflammation and metabolism: implications for diabetes and metabolic functions

Diabetes is a growing global problem, with hundreds of millions of people living with the disease worldwide. Diabetes can be divided into two major subtypes, autoimmune type 1 diabetes (T1D), and type 2 diabetes (T2D), which has stronger causal links in obesity, lifestyle, and age. Although immunity and inflammation are clearly defined in T1D, it is also understood that inflammation has a role in metabolic dysregulation in T2D, inducing insulin resistance as well as affecting β-cell function, survival, and therefore insulin secretion. Cytokines and other inflammatory mediators can affect function of cells important for metabolism, most studied in adipose tissue, muscle, and pancreatic islets. Similarly, evidence shows that complement can also have positive roles in metabolic homeostasis in adipose tissue and pancreatic islets. This review will give an introduction to this field, with focus on established and emerging roles of the complement system, an arm of humoral innate immunity that has been found to have roles in metabolic homeostasis.