The Emerging Roles of IL-36, IL-37, and IL-38 in Diabetes Mellitus and its Complications

Abstract

Diabetes mellitus is a metabolic disease caused by a combination of genetics and environmental factors. The importance of the inflammatory response occurring in the pancreas and adipose tissue in the occurrence and progression of diabetes has been gradually accepted. Excess blood glucose and free fatty acids produce large amounts of inflammatory cytokines and chemokines through oxidative stress and endoplasmic reticulum stress. There is sufficient evidence that proinflammatory mediators, such as interleukin (IL)-1β, IL-6, macrophage chemotactic protein-1, and tumor necrosis factor-α, are engaged in the insulin resistance in peripheral adipose tissue and the apoptosis of pancreatic β-cells. IL-36, IL-37, and IL-38, as new members of the IL-1 family, play an indispensable effect in the regulation of immune system homeostasis and are involved in the pathogenesis of inflammatory and autoimmune diseases. Recently, the abnormal expression of IL-36, IL-37, and IL-38 in diabetes has been reported. In this review, we discuss the emerging functions, potential mechanisms, and future research directions on the role of IL-36, IL-37, and IL-38 in diabetes mellitus and its complications.