New insights into the mechanisms of islet inflammation in type 2 diabetes.

Abstract

Impaired function and reduced mass of pancreatic islet β-cells are two hallmarks of type 2 diabetes (T2D) (1,2). However, clinical onset of T2D does not occur until β-cells fail to secrete sufficient insulin to maintain normoglycemia in the face of insulin resistance (1,2). While studies performed on isolated human islets have identified multiple pathways that may contribute to β-cell failure in T2D, these studies lack the ability to investigate the initial steps that occur in vivo before or at early stages of onset of T2D and the sequence of events that result in β-cell failure in patients with T2D. Growing evidence from recent studies suggests that chronic islet inflammation, in addition to its key role in the pathogenesis of type 1 diabetes, also plays an important role in β-cell dysfunction and failure in T2D (3–9). Impaired β-cell function precedes the clinical onset of T2D, suggesting an early role for islet inflammation in the process of β-cell failure in this disease. The association between chronic activation of the innate immune system and T2D has long been appreciated (10) but recently has gained high attention due to increasing evidence supporting its importance. The elevated number of islet-associated macrophages and increased expression of interleukin (IL)-1β have been reported in the pancreatic islets …