Editorial

Insulin secretion and β-cell biology are the main theme of the Servier-IGIS Meetings that have been held yearly since 2000 in St. Jean Cap Ferrat in southern France (1–5). Previous symposia have mostly focused on insulin secretion and its relationship with β-cell defects in type 2 diabetes. Type 1 diabetes has not previously been considered, since it is generally viewed exclusively as an autoimmune disease. However, the pathophysiology of either disease is centered on β-cells, and type 1 and type 2 diabetes share many concerns, especially the goal of preserving or restoring a normal functional β-cell mass. Evidence has accumulated that immune tolerance reflects a permanent cross talk between the different cells involved in immune survey functions and peripheral tissues, as in the case of β-cells in type 1 diabetes. As in most common autoimmune diseases, the problem of the antigenic specificity of the autoimmune reaction that drives the β-cell damage has been one with most unpredictable issues over the past 20 years. Whether the activation of autoimmunity proceeds from intrinsic immune dysregulation or requires the presence of β-cells is now no longer a question. Against all predictions, the search for the “diabetes autoantigen” has resulted in a long list of candidates with rather loose identification criteria. All presently high-ranking β-cell autoantigens are defined as proteins expressed by β-cells, not as β-cell–specific antigens. Indeed, evidence has accumulated to indicate that B- and T-cells recognize many autoantigens, rather than a single autoantigen, during diabetes development and that most autoantigens are not β-cell specific. This makes type 1 diabetes a β-cell disease rather than an antigen-specific immune disease. As for type 2 diabetes, there is overwhelming evidence that it cannot be considered exclusively from the angle of the β-cell. β-Cells are at the center of multiple physiological loops that send …