Descriptive and Mechanistic Considerations of Interleukin 1 and Insulin Secretion

Insulin-dependent diabetes mellitus (IDDM) may be mediated in part by an autoimmune mechanism, as suggested by associated cytologie and serologie phenomena, e.g., insulitis, β-cell necrosis, and the presence of both islet cell and insulin antibodies. Immunological approaches to the prediction and intervention in the progression of β-cell destruction in this disease are under evaluation. A recent hypothesis is that cytokines, including interleukin 1 (IL-1), play causative roles in such autoimmune processes. Several studies have convincingly demonstrated that IL-1 is a potent modulator of β-cell function and can potentiate or inhibit glucose-induced insulin secretion, depending on the concentration and length of exposure to IL-1. IL-1 alone or in concert with other cytokines is cytotoxic to β-cells. The cellular mechanisms responsible for the potent effects of IL-1 on the β-cell are unknown and just beginning to emerge. Although speculative at this time, this perspective delineates cellular mechanisms that are likely to represent possible primary sites for the IL-1 action on β-cells. A mechanistic understanding of the effects of IL-1 on the β-cell may clarify its role in modulating insulin release in vivo or yield insight into the pathogenesis of IDDM.