The HLA‐IDDM association: Implications for etiology and pathogenesis of IDDM

Ceramide inhibits pancreatic β‐cell insulin production and mitogenesis and mimics the actions of interleukin‐1β

“…Similar effects were recorded in this study, and in many previous reports [1,5,6,10,13,17,18], by exposure to the cytokine IL-lfl. There is much converging evidence to support a key effector role for IL-lfl in the development of type-1 diabetes mellitus.…”

“…Fax: (46) (87) 293 658. ever, far less attention has been paid to the factors that inhibit fl-cell function and mitosis, in spite of the fact that such factors may be of regulatory significance. Nonetheless, much interest has been focused on interleukin-lfl (IL-lfl), a cytokine known to be produced by islet-infiltrating macrophages preceding the onset of type-1 diabetes mellitus [5]. IL-lfl exerts cytotoxic and suppressive actions on the fl-cell in vitro and is believed to occupy a pivotal role in triggering the outbreak of type-1 diabetes mellitus which is characterized by progressive necrosis of the fl-cells by autoimmune processes [5,6].…”

Interleukin‐1 induces rapid and transient expression of the c‐fos proto‐oncogene in isolated pancreatic islets and in purified β‐cells

“…Although the molecular mechanisms which contribute to the pathogenesis of IDDM are not yet understood, a recent hypothesis is that the soluble immune mediator, interleukin 1 (IL-1), plays a role in the destruction of pancreatic d-cells that is the hallmark pathologic lesion of the disease [2]. IL-1, alone or in concert with other cytokines, has been reported to cause lysis of d-cells in vitro under some conditions [3][4][5][6].…”

Lack of association of T cell receptor beta-chain constant region polymorphism with insulin-dependent diabetes mellitus in Finland

“…There are indications that an autoimmune process is involved in the pathogenesis of insulin-dependent diabetes mellitus (IDDM), the major susceptibility alleles for the disease being located in the HLA-DR/DQ region (Owerbach et al, 1983;Cohen-Haguenauer et ai, 1985;Nerup, Mandrup-Poulsen & Molvig, 1987;Todd, Bell & McDevitt, 1987), The difference in concordance rate between HLA-identical siblings (16-25%) (Gorsuch et al, 1982;Tarn et al, 1988) versus monozygotic twins (30-50%) (Barnett et al, 1981;Olmos et al, 1988) nevertheless suggests that genes other than those for HLA may be involved in determining the risk of contracting the disease. Thus interest has been focused recently on the other genes coding for the key molecules in the immunological reactions.…”