Reduced β-cell numbers and function (β-cell failure) contribute to essentially all forms of diabetes, and must be corrected if established disease is to be cured. Current therapies have been shown not to prevent β-cell failure and the availability of insulin-secreting cells for replacement-based therapies is severely restricted. Researchers have responded to this challenge by aiming to generate new β-cells (or β-like cells) in vitro or potentially in situ, by diverse strategies including manipulation of stem cells, β-cells, or even non- β-cells such as hepatocytes. Which ever approach is ultimately most successful is at present not known, what is certain is that progress will needs to be informed by a deeper understanding of those cellular processes which determine β-cell differentiation, renewal and survival. Interest in this approach has been fuelled by the remarkable capacity for β-cell replication and renewal demonstrated in many model systems. Potential regulatory factors have already been identified and include various proteins required for promoting the G1/S transition of the cell cycle, including c-Myc and downstream transcriptional targets such as cyclin D and E2F family members. It is likely that for these factors to be exploited therapeutically, that we will need to circumvent the inherent tumor suppressor activity associated with aberrant activity of these proteins, including avoidance of apoptosis and growth arrest. Much recent work has begun to unravel the complexity of growth-regulating networks in which these proteins are involved and there is reason for future optimism.
Keywords: c-Myc, islet of langerhans, transgenic mice, pancreas, diabetes mellitus
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