Coping with diabetes requires frequent and even today mostly invasive blood glucose-based monitoring. Partly due to this invasive nature and the associated reduced skin wound healing and increased risk of infection, non-invasive glucose monitoring technologies would represent considerable progress. Edited keratinocytes may enable such a function.
Proteomics analysis
We identified Trisk 95 as the only protein whose expression is induced in response to high blood glucose. A luciferase reporter assay demonstrated that induction of Trisk95 expression occurs not only at the protein level but also transcriptionally. This induction was associated with a marked elevation in the Fluo-4 signal, suggesting a role for intracellular calcium changes in the signalling cascade. Strikingly, these changes lead concurrently to fragmentation of the mitochondria. As judged from the knockout findings, both the calcium flux and the mitochondrial phenotype were dependent on Trisk95 function, since the phenotypes in question were abolished.
The data demonstrate that the skin represents an organ that reacts robustly and thus mirrors changes in systemic blood glucose levels. The findings are also consistent with a channelling model of Trisk95 that serves as an insulin-independent but glucose-responsive biomarker taking part in releasing calcium from the cellular stores in the skin. The skin cells may thus provide a novel mean for glucose monitoring when analysing changes in labelled Trisk95 and calcium. By that, this study is the first proof of the concept of our registered patent (No. PCT FI2016/050917), which proposes the use of cells as biosensors for developing personalized health-monitoring devices.