New Insulin Molecule Can Self-Adjust According To Blood Sugar Level Of Patient: Study
A glucose responsive insulin (GRI) that responds to changes in blood sugar concentrations has remained an elusive goal.
Researchers from the University of Copenhagen and biotech firm Gubra have developed a new insulin molecule that will make blood sugar regulation both easier and safer for those with type 1 diabetes.
With new discovery hopefully everyday life for the more than 46 million people around the world who suffer from type 1 diabetes could become much easier and safer.
The new insulin molecule, in the future, will ensure that diabetics receive just the right amount of insulin.
The insulin on the market today is unable to identify whether a patient with type 1 diabetes needs a small or large effect from the insulin, which lowers blood sugar. "That is why we have developed the first step towards a kind of insulin that can self-adjust according to a patient's blood sugar level. This has tremendous potential to vastly improve the lives of people with type 1 diabetes," explains Professor Knud J. Jensen, of the University of Copenhagen's Department of Chemistry, one of the researchers behind a new study on this new insulin.
Type 1 diabetes can present in infants as young as 6 months:
Study The researchers behind the study developed a type of insulin with a built-in molecular-binding that can sense how much blood sugar is in the body. As blood sugar rises, the molecule becomes more active and releases more insulin. As blood sugar drops, less is released.
"The molecule constantly releases a small amount of insulin, but varies according to need," says Knud J. Jensen, who continues: "It will give type 1 diabetes patients a safer and easier treatment. Today, a person with type 1 diabetes must inject themselves with insulin many times throughout the day and frequently monitor their blood sugar level by pricking their finger with a blood glucose meter.
This here, allows a person to inject the new insulin molecule less often over the course of a day and thereby think about it less," says Knud J. Jensen.
Although the new 'automated' insulin is a major advance towards better diabetes treatment, it will be a while before the revolutionary insulin becomes a part of diabetics' everyday lives. "We've tested the insulin molecule on rats and it has proven itself effective. The next step is to develop the molecule so that it works more rapidly and accurately. And finally, to test it in humans -- a process that can take many years.
But it is certainly worth pinning one's hopes on," explains Professor Jensen. The idea to create a kind of insulin that self-adjusts to a patient's needs occurred many years ago, while Professor Jensen was living in the United States.
This is where a friend of his with type 1 diabetes recounted to him a story: "My author friend Jan Sonnergaard told me about a married couple who had been dancing one night. The man had type 1 diabetes and was feeling unwell. The wife thought to stabilise his blood sugar by giving him insulin. Unfortunately, the insulin eventuated in her husband's death because he had hypoglycemia, low blood glucose, before the insulin injection. I wanted to make certain that this kind of tragedy would never be repeated," says Knud J. Jensen, concluding: "The difficult thing with diabetes is that insulin always works the same way. It lowers blood sugar, even though that might not be what a patient requires. This is what we seek to address with our new molecule.


Full Paper

An Aldehyde Responsive, Cleavable Linker for Glucose Responsive Insulins

Knud J. Jensen 

Karin Mannerstedt 

Narendra Kumar MIshra 

et al

First published: 10 November 2020



A glucose responsive insulin (GRI) that responds to changes  in blood glucose concentrations has remained an elusive goal. Here we describe the development of glucose cleavable linkers based on hydrazone and thiazolidine structures. We developed linkers withlow levels of spontaneous hydrolysis but increased level of hydrolysis with rising concentrations of glucose, which demonstrated their glucose responsiveness  in vitro . Lipidated hydrazones and thiazolidines were conjugated to the LysB29 side‐chain of HI by pH‐controlled acylations providing GRIs with glucose responsiveness confirmed  in vitro for thiazolidines. Clamp studies showed increased glucose infusion at hyperglycemic conditions for one GRI indicative of a true glucose response. The glucose responsive cleavable linker in these GRIs allow changes in glucose levels to drive the release of active insulin from a circulating depot. We have demonstrated an unprecedented, chemically responsive linker concept for biopharmaceuticals.

The article


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