Insulin derivative activated by molecular switch responds to glucose challenge

Insulin molecular structure pictured. Researchers have synthesised an insulin derivative that is activated by a molecular switch that responds to blood glucose.

Self-administered insulin is the mainstay of treatment for type 1 diabetes. However, most insulin-dependent patients suffer from complications due to poor adherence or inadequate glycaemic control.

To overcome these issues, US researchers synthesised an insulin derivative that is activated by a molecular switch that responds to blood glucose. When administered in a diabetic mouse model, the modified insulin responded to a glucose challenge more rapidly than either standard insulin or a long-acting insulin formulation (insulin detemir).

The responsiveness of the modified insulin was similar to that of a healthy pancreas and some derivatives were able to respond to repeated glucose challenges over a 13-hour period. The new insulin represents a step “toward the generation of more autonomous therapy with improved blood glucose control”, the researchers conclude in PNAS (online, 9 February 2015)[1]
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Smart, glucose-responsive insulin

Source: Matthew Webber

When blood sugar is high, the insulin derivative, called Ins-PBA-F, becomes active. One injection can repeatedly normalise blood sugar levels over a minimum of 14 hours in mice with a type 1 diabetes-like condition

References

[1] Chou DH-C, Webbera MJ, Tang BC et al. Glucose-responsive insulin activity by covalent modification with aliphatic phenylboronic acid conjugates. PNAS 2015. doi:10.1073/pnas.1424684112.

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Citation
The Pharmaceutical Journal, PJ, 14 February 2015, Vol 294, No 7849;294(7849):DOI:10.1211/PJ.2015.20067827