Diabetes mellitus and apoptosis: inflammatory cells

Abstract

Since the early observation that similarities between thyroiditis and insulitis existed, the important role played by inflammation in the development of diabetes has been appreciated. More recently, experiments have shown that inflammation also plays a prominent role in the development of target organ damage arising as complications, with both elements of the innate and the adaptive immune system being involved, and that cytokines contributing to local tissue damage may arise from both infiltrating and resident cells. This review will discuss the experimental evidence that shows that inflammatory cellmediated apoptosis contributes to target organ damage, from beta cell destruction to both micro-and macro-vascular disease complications, and also how alterations in leukocyte turnover affects immune function.

Upregulation of PTEN by peroxynitrite contributes to cytokine-induced apoptosis in pancreatic β-cells

“…Proinflammatory cytokines (such as IL-1b, TNF-a, and IFN-c) released during this autoimmune response are regarded as important mediators of b-cell apoptosis [28]. Recently, inflammatory mediators have been increasingly implicated in type 2 diabetes development [29][30][31]. These data strongly suggest that cytokine signaling blockade may be a potential method for preventing diabetic b-cell loss.…”

Wld S protects against peripheral neuropathy and retinopathy in an experimental model of diabetes in mice

“…Much of our understanding of the role of the T cell-mediated autoimmune mechanism has come from the use of animal models. Autoreactive T cells produce inflammatory cytokines, which can upregulate Fas expression on beta cells and stimulate production of nitric oxide and reactive oxygen species, inducing caspase-3-dependent apoptotic signalling cascades [1,2]. With the excessive DNA damage resulting from reactive oxygen species accumulation, poly(ADP-ribose) polymerase (PARP) is highly activated.…”

The Impact of Inflammation on Pancreatic β-Cell Metabolism, Function and Failure in T1DM and T2DM: Commonalities and Differences

“…These cytokines aid in the recruitment of patrolling macrophages, which may subsequently become activated by high microenvironment levels of IL-1β and amplify IL-1β content in their own right [76]. In terms of islet inflammation, IL-1β expression and its effects on β-cell death appears to be a uniting factor, in both T1 and T2DM and is being considered a possible therapeutic target [77,89].…”

“…Infiltration of cytotoxic T-cells in T1DM has been well characterised [82]. Therefore, some developing treatment strategies for this precise component of T1DM disease is the generation of T-cell targeted therapy to prevent the destruction of transplanted islets, some of which include introduction of anti-inflammatory Tregs that regulate T-cell activation [89]. Since inflammation has been detected in T2DM, these approaches may have similar applications.…”