Modified Insulin with On-Off Switch May Prevent Sudden Hypoglycemic Episodes in Diabetics: Study Finds
Modified insulin that can prevent sudden drops in blood sugar has been demonstrated in laboratory experiments and animal models, reports a paper in Nature. This could provide a more flexible way to supplement insulin for individuals with diabetes and reduce sudden drops in blood glucose.
Researcher Rita Slaaby and colleagues present a modified form of insulin with activity that varies according to glucose levels in the blood. The molecule, named NNC2215, is equipped with a switch that can open and close in response to glucose. Under high glucose concentrations, the switch opens, and the insulin becomes more active, removing glucose from the blood. When glucose levels decrease, the switch moves to a closed state, which prevents glucose uptake.
Laboratory experiments showed that upon an increase in glucose concentration from 3 to 20 mM, the NNC2215 insulin receptor affinity increased by 3.2-fold, validating its potential to respond to changes in blood glucose levels. In rat and pig models of diabetes, NNC2215 proved to be as effective as human insulin in lowering blood glucose. Its increased glucose sensitivity was shown to protect against hypoglycemia in these animal subjects.
This modified insulin may aid in preventing the sharp drops in glucose that can severely affect individuals with diabetes, especially during sleep. This could improve both long- and short-term complications associated with diabetes, the authors note.
Reference: Hoeg-Jensen, T., Kruse, T., Brand, C.L. et al. Glucose-sensitive insulin with attenuation of hypoglycaemia. Nature (2024). https://doi.org/10.1038/s41586-024-08042-3
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