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Comment
. 2014 Feb;57(2):265-9.
doi: 10.1007/s00125-013-3114-7. Epub 2013 Nov 21.

Good news for the ageing beta cell

Aaron Bender  1 , Andrew F Stewart
Affiliations
Comment

Good news for the ageing beta cell

Aaron Bender et al. Diabetologia. 2014 Feb.
No abstract available

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Conflict of interest statement

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Figures

Fig. 1
Fig. 1
The Yin and Yang of PI3K vs PTEN in the regulation of beta cell proliferation. This is a greatly oversimplified schematic of the receptor-to-PI3K-to-proliferation pathway, focusing on PI3K (in green, because it activates the mitogenic pathway) and PTEN (in red because it inhibits the mitogenic pathway). In this example, a GPCR (such the GLP-1 receptor) activates PI3K via a G-protein (such as Gq); or a tyrosine kinase receptor, such as the insulin receptor (IR) or IGF-1 receptor (IGFR) activates PI3K via adaptor proteins, or in some cases directly. This leads to a sequence of downstream events including generation of PIP3, its activation of PDK1, which phosphorylates Akt/PKB, which in turn phosphorylates, thereby inhibiting, TSC1 and 2; this releases the small G-protein, Rheb, so that it can phosphorylate and activate MTOR. Active MTOR, through a complex series of downstream events, leads to proliferation. Not shown in the figure, this pathway interacts with a variety of other mitogenic and survival pathways, including, but not limited to, the Ras/Raf/MAPK pathways, JAK–STAT signalling pathways and PKC signalling pathways. For readers who prefer more detail, Shi et al [17] provide illustrations of PTEN intracellular compartmentalisation and regulation of its levels and activity. In the context of the accompanying report by Yang et al [13], the key point is that PTEN is placed near the top of this pathway, and thus in a pivotal position for controlling the entire pathway. It balances the pro-mitogenic activity of PI3K: its loss is permissive for increased activity in the pathway (and thus proliferation); conversely, its overexpression inhibits the pathway, reducing proliferation, and serving as a tumour suppressor protein (inhibiting proliferation)
See this image and copyright information in PMC

Comment on

References

    1. Teta M, Long SY, Wartschow LM, Rankin MM, Kushner JA. Very slow turnover of beta-cells in aged adult mice. Diabetes. 2005;54:2557–2567. - PubMed
    1. Meier JJ, Butler AE, Saisho Y, et al. Beta cell replication is the primary mechanism subserving the postnatal expansion of beta cell mass in humans. Diabetes. 2008;57:1584–1594. - PMC - PubMed
    1. Kassem SA, Ariel I, Thornton PS, Scheimberg I, Glaser B. Beta cell proliferation and apoptosis in the developing normal human pancreas and in hyperinsulinism of infancy. Diabetes. 2000;49:1325–1333. - PubMed
    1. Gregg BE, Moore PC, Demozay D, et al. Formation of a human beta cell population within pancreatic islets is set early in life. J Clin Endocrinol Metab. 2012;97:3197–3206. - PMC - PubMed
    1. Levitt HE, Cyphert TJ, Pascoe JL, et al. Glucose stimulates human beta cell replication in vivo in human islets transplanted into NOD-SCID mice. Diabetologia. 2011;54:572–582. - PMC - PubMed

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