Islet Inflammation Impairs the Pancreatic β-Cell in Type 2 Diabetes

Abstract

Onset of Type 2 diabetes occurs when the pancreatic beta-cell fails to adapt to the increased insulin demand caused by insulin resistance. Morphological and therapeutic intervention studies have uncovered an inflammatory process in islets of patients with Type 2 diabetes characterized by the presence of cytokines, immune cells, beta-cell apoptosis, amyloid deposits, and fibrosis. This insulitis is due to a pathological activation of the innate immune system by metabolic stress and governed by IL-1 signaling. We propose that this insulitis contributes to the decrease in beta-cell mass and the impaired insulin secretion observed in patients with Type 2 diabetes.

The Analgesic, Anti-Inflammatory and Anti-Pyretic Activities of Tinospora cordifolia

“…Pain, fever and inflammation are not considered major diseases, but are common clinical manifestations associated with many fatal diseases [27]. Inflammation plays a crucial role in the pathogenesis of many auto-immune diseases [28][29][30][31][32][33]. Naturally occurring anti-inflammatory agents have shown anti-inflammatory activities against various autoimmune diseases [34][35][36][37][38][39][40][41][42].…”

Metabolic effects of high‐dose prednisolone treatment in early rheumatoid arthritis: Balance between diabetogenic effects and inflammation reduction

“…The acute-phase protein CRP was similarly shown to induce insulin resistance by impairment of insulin signaling in an animal model (31). Importantly, proinflammatory cytokines have recently been shown to induce beta cell dysfunction (32). In addition, chronic inflammation may reduce beta cell mass by stimulating apoptosis of beta cells (33).…”

The identification of TNFR5 as a therapeutic target in diabetes

“…Crucially however, new findings [4] indicate that it is pancreatic upregulation of the tumor necrosis factor receptor superfamily member, TNFR5 (also known as cluster of differentiation 40 (CD40), that leads to activation of the transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 1 (STAT1) that drive islet inflammation that ultimately induces β-cell death [5][6][7]. Furthermore, inhibition of TNFR5 signaling though selective RNA interference abrogates glucolipotoxic induction of NF-κB and STAT1 activation [4].…”