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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)
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