From Beta Cell Impairment and Destruction to Multiple Organ Lesions in Diabetes: Extent of the Problem
The characteristic lesion—insulitis—in the islets of Langerhans at the time of diagnosis of insulin-dependent diabetes mellitus (IDDM) comprises a lymphocytic filtration in the islets occurring together with selective destruction of the beta cells . This finding clearly indicates that immunologic mechanisms may be at work. A wide range of autoimmune phenomena has been described in newly diagnosed IDDM patients  and may also be present before IDDM becomes clinically manifest . Human lymphoid cells  and antibodies  from IDDM patients have been shown to interfere with beta cell function, but evidence that shows a direct cytotoxic effect is lacking. Furthermore, two recent observations make a direct pathogenetic role of islet cell antibodies unlikely: (a) cyclosporine-A-induced remission of endogenous insulin production in newly diagnosed IDDM patients was independent of the presence or absence of islet cell antibodies ; and (b) islets in segmental pancreatic grafts exchanged between identical twins discordant for IDDM showed insulitis, but no antibody deposition, in the islets, and occurrence of IDDM in the recipients had no correlation to circulating islet cell antibodies . That beta cells may be destroyed by cytotoxic T-lymphocytes is the other obvious possibility. It has, however, been demonstrated that beta cell destruction is not MHC restricted when grafting MHC-incompatible nonrejectable culture-conditioned islets in animals with diabetes-like syndroms, e.g., in the BB rat and the NOD mouse .
KeywordsBeta Cell Diabetic Nephropathy Glomerular Basement Membrane Islet Cell Antibody Persistent Proteinuria
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