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 cytologic and serologic phenomena, e.g., insulitis, beta-cell necrosis, and the presence of both islet cell and insulin antibodies. Immunological approaches to the prediction and intervention in the progression of beta-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 beta-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 beta-cells. The cellular mechanisms responsible for the potent effects of IL-1 on the beta-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 beta-cells. A mechanistic understanding of the effects of IL-1 on the beta-cell may clarify its role in modulating insulin release in vivo or yield insight into the pathogenesis of IDDM.
D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D002118:Calcium / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007330:Insulin Antibodies / Q000032:analysis; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000502:physiology*; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008970:Molecular Weight; D011494:Protein Kinases / Q000378:metabolism
D001323:Autoantibodies; D007328:Insulin; D007330:Insulin Antibodies; D007375:Interleukin-1; D011494:Protein Kinases; D005947:Glucose; D002118:Calcium