It is broadly accepted that the main cause of type 2 diabetes is overfeeding. Unclear is how this metabolic stress is translated into signals leading to defective insulin secretion and action. Increasing evidence points to a role of the innate immune system in sensing changes in nutrient levels. This results in an inflammatory process that has been proposed to contribute to the pathogenesis of type 2 diabetes (1). At the origin of this process, activation of the IL-1 pathway seems to play a central role. Processing of pro-IL-1 to IL-1 is controlled by the inflammasome (see below) as a response to sensing danger signals. In this issue of Endocrinology, Youm and colleagues (2) demonstrates that the inflammasome mediates islet inflammation induced by high-fat feeding. Activation of the innate immune system is the first response to tissue injury or aggression. It is characterized by release of cytokines and chemokines and immune cell invasion and is accompanied by functional or structural damage followed by tissue repair or fibrosis. This inflammatory process was originally thought to be caused by microbes or physical damages. However, in some cases, the innate immune system may attack the body’s own tissues in the absence of an exogenous aggressor, resulting in a sterile inflammatory process, i.e. an autoinflammatory disease. In the pancreatic islet, metabolic stress may also elicit such a response. Indeed, glucose, free fatty acids, and human islet amyloid polypeptide may induce IL-1 , launching a proinflammatory response impairing insulin production and secretion (3–6). Accordingly, blocking IL-1 improves insulin release and glycemia in prediabetic and diabetic patients (7, 8). The question arises of how metabolic stress is sensed by the IL-1 system. The inflammasome is a key factor mediating activation of innate immunity. It is a complex of several proteins that may activate caspase 1, which cleaves pro-IL-1 to IL-1 . Activation of IL-1 will then induce itself and a variety of cytokines and chemokines via nuclear factorB. Interestingly, the inflammasome can be activated by a variety of metabolic disturbance including uric acid during gout arthritis (9) and cholesterol in atherogenesis (10). In the context of diabetes, it has been shown that glucose and human islet amyloid polypeptide activates the inflammasome in pancreatic islets (5, 6, 11) and lipopolysaccharide, free fatty acids, and ceramides in adipose tissues (12–14). All of this assigns to the inflammasome a role as a sensor of metabolic stress. The above mentioned studies have convincingly shown the functional role of the inflammasome in insulin resistance (12–14). With respect to islet inflammation, animal and clinical studies have shown that reducing IL-1 activity improves insulin secretion (7, 8, 15, 16). However, it remained to be demonstrated that this involves the inflammasome. In the study by Youm and colleagues (2), it is shown that lack of the NLRP3 inflammasome protects from the development of islet fibrosis in mice on a high-fat diet. Because fibrosis is an end stage of a chronic inflammatory process, it may be assumed that the level of insulitis was decreased, although data on immune cell infiltration are missing in this study. Another weakness of the study is the lack of functional insulin secretion tests. However, islet mass and insulin release were improved in the NLRP3 knockout mice on a high-fat diet compared with wildtype controls. Therefore, it can be concluded that inflammasome is most probably a critical mediator of islet inflammation in obesity.