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Engineering beta cell mass regulation in diabetes

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?-cell failure, encompassing a range of aberrant cellular processes from dysfunction to death, has long been recognised as the central defect in Type 1 Diabetes Mellitus (T1DM), but is now also accepted as a major factor in essentially all other types of diabetes, notably the “epidemic” variant, Type 2 Diabetes (T2DM). However, the mechanisms involved differ as exemplified by prominent role ascribed to the immune system and extrinsic pathway of apoptosis in T1DM and to metabolic insults (gluco- and lipo- toxicity) in T2DM. Intriguingly, common ground is emerging, whereby ?-cell renewal, death and plasticity are influenced by combinations of environmental factors, including metabolic changes, immune processes, cell-cell contacts and growth factors acting on ?-cells rendered either resistant or prone to cell death by intracellular signaling pathways, such as the IRS2/PI3K/AKT/mTOR pathway and master regulatory proteins such as c-Myc. Moreover, maintaining a functional ?-cell mass does not merely require avoiding destruction and dysfunction, but also renewal by self-replication and/or differentiation from precursors. Finally, the fact that processes regulating growth and death are intimately linked and also impact on function creates intriguing conundrums- for instance is there a maximum number/proportion of ?-cells that can be replicating at any one time without compromising ability to control blood glucose. This is very pertinent as rising glucose could accelerate ?-cell losses and or further compromise renewal thus constituting a spiral to catastrophe and transition from compensated insulin resistance to overt diabetes. Important new therapies are exploiting knowledge of beta cell mass regulation and function and further advances may finally unleash the potential of ?-cell targeted treatments and even cell-based therapies for diabetes. This exciting area will be the focus of this review.

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Young, James, Pelengaris, Stella, Chipperfield, Andrew, Heath, William and Khan, Michael (2008) Engineering beta cell mass regulation in diabetes Current Topics in Biochemical Research, 10, (1), pp. 47-78.

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Published date: 2008


Local EPrints ID: 66454
ISSN: 0972-4583
PURE UUID: 91d68814-54f1-48a9-9c83-ec81c30f13b2
ORCID for Andrew Chipperfield: ORCID iD

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Date deposited: 22 Jun 2009
Last modified: 19 Jul 2017 00:24

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Author: James Young
Author: Stella Pelengaris
Author: William Heath
Author: Michael Khan

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