Inflammation is a characteristic of ageing and many chronic degenerative disorders, such as atherosclerosis, dementia, and autoimmune and metabolic diseases. Inflammatory mechanisms are involved in the pathogenesis of Type 1 and Type 2 diabetes and in causing insulin resistance, beta-cell failure and late diabetic complications. Despite promising preclinical evidence supporting a direct causative role of inflammatory mediators in insulin resistance, so far only agents that also inhibit formation of reactive oxygen species, e.g. salicylates improve insulin sensitivity in clinical trials, whereas specific biologic inhibitors of inflammatory cytokines e.g. TNF, IL-1 or IL-6 have so far failed. In contrast, anti-IL-1 therapy in Type 2 diabetic patients and anti-TNF treatment in recent-onset Type 1 diabetic patients improve glycemia and beta-cell function. This presentation will focus on recent studies of the role of divalent metal transport in b-cell function and response to inflammatory assault in vitro and in vivo.

References: 

Larsen CM et al N Engl J Med356;1517–26, 2007; Donath M & Mandrup-Poulsen T Nature Clin Pract Endocrinol Metab4: 240–241, 2008; Larsen CM et al Diabetes Care32; 1663–68, 2009; Mandrup-Poulsen T et al Nature Rev Endocrinol 6: 158–66, 2010; Dinarello CA et al Curr Opinion Endocrinol DiabObesity 17: 314–21, 2010; Donath MY & Shoelson SE Nature Rev Immunol, 11, 98–107, 2011