Inceptor binds to and directs insulin towards lysosomal degradation in β cells.

Blunted first-phase insulin secretion and insulin deficiency are indicators of β cell dysfunction and diabetes manifestation. Therefore, insights into molecular mechanisms that regulate insulin homeostasis might provide entry sites to replenish insulin content and restore β cell function. Here, we identify the insulin inhibitory receptor (inceptor; encoded by the gene IIR/ELAPOR1) as an insulin-binding receptor that regulates insulin stores by lysosomal degradation.

Patterned thin film enzyme electrodes spincoating and glutaraldehyde vapor crosslinking: towards scalable fabrication of integrated sensor-on-CMOS devices.

Effective continuous glucose monitoring solutions require consistent sensor performance over the lifetime of the device, a manageable variance between devices, and the capability of high volume, low cost production. Here we present a novel and microfabrication-compatible method of depositing and stabilizing enzyme layers on top of planar electrodes that can aid in the mass production of sensors while also improving their consistency. This work is focused on the fragile biorecognition layer as that has been a critical difficulty in the development of microfabricated sensors.

Inceptor counteracts insulin signalling in β-cells to control glycaemia.

Resistance to insulin and insulin-like growth factor 1 (IGF1) in pancreatic β-cells causes overt diabetes in mice; thus, therapies that sensitize β-cells to insulin may protect patients with diabetes against β-cell failure. Here we identify an inhibitor of insulin receptor (INSR) and IGF1 receptor (IGF1R) signalling in mouse β-cells, which we name the insulin inhibitory receptor (inceptor; encoded by the gene Iir). Inceptor contains an extracellular cysteine-rich domain with similarities to INSR and IGF1R, and a mannose 6-phosphate receptor domain that is also found in the IGF2 receptor (IGF2R).

Development of a microarray-based assay for efficient testing of new HSP70/DnaK inhibitors.

A facile method for testing ATP binding in a highly miniaturized microarray environment using human HSP70 and DnaK from Mycobacterium tuberculosis as biological targets is reported. Supported by molecular modelling studies we demonstrate that the position of the fluorescence label on ATP has a strong influence on the binding to human HSP70. Importantly, the label has to be positioned on the adenine ring and not to the terminal phosphate group.