Activation of the transcription factor nuclear factor-B (NF-B) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-B in vitro, we observed a long-lasting sustained activation of NF-B in the absence of decreased IB␣ in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-Bp65. A comparable increase in NF-Bp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-␤ peptide ( T issue culture models of cellular activation provide easily accessible systems for detailed analysis of mechanisms potentially underlying the pathogenesis of human disease. However, the time course of such in vitro models is usually significantly abbreviated, limited to hours to days, compared with the pace of disorders under study in vivo. This indicates the importance of seeking out mechanisms in cell culture that might bridge the gap that accounts for the chronicity of cellular perturbation observed in the intact organism.The transcription factor nuclear factor-B (NF-B) has been proposed as a critical bridge between oxidant stress and gene expression (1-8). Exposure of cells to inflammatory, infectious, or other stressful stimuli results in rapid phosphorylation and degradation of IB␣ and the subsequent release and translocation of NF-B into the nucleus (1-11). This mechanism ensures quick and finely tuned cellular responses in the absence of de novo protein synthesis. Because transcription of IB␣ is positively autoregulated by NF-B (9 -11), activation of NF-B is usually self-terminated within minutes to hours (1-11). Such a scenario lends itself to analysis by short-term in vitro studies in which stimulus-induced responses are transient and the system returns to the baseline state over hours. Consequently, induction of NF-B and enhanced transcription of its target genes in vitro have been studied mainly in the setting of acute cellular responses.Reactive oxygen intermediates are generated by processes that occur over seconds. However, increasing evidence suggests a role for oxidative stress in chronic degenerative diseases such as atherosclerosis (1,6,12,13), diabetes (14 -16), and Alzheimer's disease (17)(18)(19). This indicates the relevance of signal transduction systems such as NF-B, which are capable of transforming the appearance and disappearance of short-lived oxygen free radicals into more sustained signals for cellular activation

With a controlled insulin therapy and a resulting well-compensated diabetic metabolic state, mineralization and cellular differentiation disorders, as well as the decreased values of biomechanical properties in the fracture repair in the poorly compensated diabetic metabolic state with very severe hyperglycemia can be avoided.

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