Cell-based therapies for treating insulin-dependent diabetes (IDD) can provide a more physiologic regulation of blood glucose levels in a less invasive fashion than daily insulin injections. Promising cells include non-beta cells genetically engineered to secrete insulin in response to physiologic cues; responsiveness can be introduced at the transcriptional level to regulate preproinsulin (PPI) mRNA biosynthesis. However, these cells exhibit sluggish secretion dynamics, which is not appropriate for achieving euglycemia in higher animals and, eventually, humans. In this work, we have engineered the PPI mRNA so as to destabilize it through nonsense-mediated mRNA decay (NMD). When expressed under transcriptional regulation in HepG2 hepatomas, the engineered PPI mRNA level and of the insulin secretion rate declined faster upon switching off transcription, compared to the one-copy non-engineered control. Our work provides a simple and straightforward method to improve the dynamics of transcriptionally regulated insulin secretion, which can be a useful tool in developing cell-based therapies for IDD.
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 May 2021.
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#7,501,789
of 34,575,175 outputs
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#4,010
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#28,974
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Outputs of similar age from Febs Letters
#29
of 135 outputs
Altmetric has tracked 34,575,175 research outputs across all sources so far. Compared to these this one has done well and is in the 78th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 17,653 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one has done well, scoring higher than 77% of its peers.
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We're also able to compare this research output to 135 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.
