Islet inflammation in type 2 diabetes

Abstract

Metabolic diseases including type 2 diabetes are associated with meta-inflammation. β-Cell failure is a major component of the pathogenesis of type 2 diabetes. It is now well established that increased numbers of innate immune cells, cytokines, and chemokines have detrimental effects on islets in these chronic conditions. Recently, evidence emerged which points to initially adaptive and restorative functions of inflammatory factors and immune cells in metabolism. In the following review, we provide an overview on the features of islet inflammation in diabetes and models of prediabetes. We separately emphasize what is known on islet inflammation in humans and focus on in vivo animal models and how they are used to elucidate mechanistic aspects of islet inflammation. Further, we discuss the recently emerging physiologic signaling role of cytokines during adaptation and normal function of islet cells.

Keywords: Cytokines; IL-1β; Insulin; Islet inflammation; Type 2 diabetes; β-Cell.

Fig. 1

In physiology, resident macrophages and cytokines have a homeostatic role in the development and function of islet β-cells. T2D is associated with chronic, low-grade inflammation in pancreatic islets. Insulitis is characterized by an elevated number of proinflammatory macrophages and increased levels of cytokines and chemokines and contributes to impaired islet function. Depletion of macrophages and inhibition of the IL-1 system in islets reduces macrophage infiltration and proinflammatory cyto- and chemokine expression and improves insulin secretion