A Relevant Phenomenon in Early IDDM?

Most studies dealing with the pathogenesis of IDDM have emphasized the immune assault against f3-cells. In this perspective, we review the data that suggest that the @-cell destruction of IDDM depends on a balance between @-cell damage and repair. The progressive @-cell damage leading to iDDM seems to follow markedly different temporal courses in individual patients. Some individuals at high risk for developing IDDM, and presenting with impaired @-cell function, appear to recover pcel l function when followed prospectlveiy. Moreover, after the clinical onset of IDDM, most patients experience a transitory period of Improved insulin secretion. In vltro and in vivo experimental data suggest that @-cells are indeed able to repair themselves after damage. Dispersed @-cells or whole islets can survive and regain their function after a toxic assault. Furthermore. the triggered by p-cells. Some of the @-cell responses to injury Include expression of heat shock proteins 32,000, 65,000, 70,000, and 90,000 hf,, activation of the enzyme poly(ADP-ribose) polymerase, induction of the growth arrest and DNA damage inducible genes 45 and 153, and enhanced manganese superoxide dlsmutase activity. The heat shock protein 70 is of special interest because it has been shown to be both Induced by interleukin-1 and protective of pcells against the deleterious effects of this cytoklne. The findings mentioned above suggest that repair mechanisms activated after @-cell injury are an important component of the IDDM disease process. It is conceivable that a detailed characterization of the cellular and molecular mechanisms involved in @-cell repair may contribute to the development of early preventive therapy for IDDM. Diabetes 42:1383-91,1993