Insulin "safety switch"

The Problem

Diabetics have high blood glucose levels due to their poor production of insulin. The main treatment is synthetic insulin injections, which bring down blood glucose levels to normal levels. The problem is, you can bring them down too far. Low blood glucose levels can lead to serious issues like fainting and even death in extreme cases.

Injected insulin often takes a while to take effect and hangs around in the bloodstream for a long time after injection. With too much insulin in their system, something as simple as working out or missing a meal can cause the patient’s glucose levels to fall dangerously low.

Scientists have been trying to develop a synthetic insulin that switches off when blood glucose levels get too low, helping to prevent or mitigate insulin-induced complications.

This week, we’ll go through a recent paper that does just that.

The Solution

In this paper, the authors created a glucose sensitive insulin molecule that becomes inactive when glucose levels dip below the healthy range.

They made their glucose switch by attaching both a glucose binding ring (macrocycle in the image above) and a glucose-like molecule (labeled glucoside above) to an insulin backbone. Blood glucose binds to the ring when there’s a healthy concentration of glucose in the blood.

But once the concentration starts to get too low, the glucose-like molecule binds to the ring. This binding causes the whole insulin molecule to rearrange, blocking the insulin from working properly by disrupting its binding to the appropriate cell receptors.

In short, the insulin shuts itself off when the glucose levels around it get too low.

The figure above compares the response of diabetic pigs to the new smart insulin (creatively named NNC2215) to a commonly used synthetic insulin, Degludec (also known as the brand name Tresiba). In this experiment, the pigs received constant doses of the two insulin treatments while the glucose amounts varied.

As you can see, the glucose levels of the smart insulin treated pigs didn’t drop as low as the Degludec treated ones. This indicates the smart insulin was able to switch itself off and prevent the glucose levels dropping too far, despite the continuous dosing.

This study provides a nice proof of concept for a smart insulin switch and some great data. I’m not sure what’s next for the tech, but I imagine the authors are working on making the switch stronger, more specific, and/or longer lasting.

See you next week for more science,

Neil