New type of insulin that switches on and off could help diabetics avoid sudden drops in blood sugar levels

October 16, 2024

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by Nature Publishing Group

A 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.

For some people with diabetes, supplementary insulin injections are needed to control blood glucose levels. Fluctuations in blood glucose levels are difficult to predict, making it hard to select the appropriate insulin doses. Even a slightly high dose can lead to hypoglycemia (blood glucose levels decreasing too much), which can be life-threatening.

Researcher Rita Slaaby and colleagues present a modified form of insulin with activity that varies according to the levels of glucose 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 (approximately the fluctuation range experienced by individuals with diabetes), 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 provide protection against hypoglycemia in these animal subjects.

This modified insulin shows promise 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.

More information: Rita Slaaby, Glucose-sensitive insulin with attenuation of hypoglycaemia, Nature (2024). DOI: 10.1038/s41586-024-08042-3

David B. Sacks, Smart insulin switches itself off in response to low blood sugar, Nature (2024). DOI: 10.1038/d41586-024-03286-5 , doi.org/10.1038/d41586-024-03286-5