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Researchers funded by the Type 1 Diabetes Grand Challenge have developed a new insulin–glucagon molecule, which could reduce dangerous drops in blood glucose, known as hypoglycaemia. For people living with type 1 diabetes, where hypoglycaemia is a constant risk, this breakthrough has the potential to make daily management safer and more reliable.
In type 1 diabetes (T1D), a person’s body doesn’t produce enough insulin, meaning blood glucose levels will continue to climb if insulin is not given (either by injection or using a pump). Managing blood glucose levels is a constant balancing act for people with type 1 diabetes, between administering the correct amount of insulin and their blood glucose going too high or too low and dealing with the consequences of this. If blood glucose goes too high, this can cause a potentially fatal complication called diabetic ketoacidosis, where a person’s blood becomes too acidic. Sustained high blood glucose levels can damage the eyes, feet, heart and kidneys. If blood glucose levels drop dangerously low it can lead to seizures, coma, and can sometimes be fatal.
Findings by US-based researchers, published in ACS Pharmacology and Translational Science, show success in engineering a product that combines both glucagon and insulin in the same molecule. Insulin is the hormone responsible for reducing blood sugars by enabling cells to use glucose for energy, and glucagon is the hormone responsible for a raising in blood glucose. This molecule was then able to take advantage of the body’s built in ‘on/off switch’ in the liver. The liver naturally responds more to insulin when glucose is high and more to glucagon when glucose is low. When blood glucose is high, the insulin part of the molecule is active, lowering blood glucose like regular insulin. However, when blood glucose is low, the glucagon part is active, signalling to the liver to release glucose and preventing low blood sugar episodes (known as hypoglycaemia or hypo).
The research team tested the new insulin in rats, with positive initial results. The insulin behaved as intended: lowered blood glucose when high and helped raise blood glucose when low – unlike regular insulin. It also reduced the need for emergency glucose injections in the rats during hypoglycaemia.
The two parts of the molecule (insulin and glucagon) worked independently but in balance, just like separate hormones. The promising results indicate that the new molecule could help lower the chance of hypoglycaemia in people with type 1 diabetes.
The study also showed that the new form of insulin stayed stable for weeks without the need for refrigeration before opening, giving it a longer shelf life than expected. This makes it more reliable for people with T1D and easier for manufacturers to produce, store, and transport.
Low blood glucose is as unpleasant side effect of type 1 diabetes. It normally occurs due to an imbalance between insulin dose, food intake and physical activity. Having a hypo is something which, if possible, all people with type 1 diabetes would want to avoid. It can be dangerous as when blood glucose is low as the brain is deprived of its energy source – glucose. This leads to a sensation of weakness, dizziness or blurred vision, alongside feeling angry or confused. There are many other potential symptoms.
This research has been funded by the Type 1 Diabetes Grand Challenge, a partnership between Breakthrough T1D, Diabetes UK and the Steve Morgan Foundation.
Michael Weiss, distinguished Professor in the Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, said:
“For the past century, coping with hypoglycaemia (the lows) has been an ever-present challenge in type 1 diabetes. This has made creating glucose-responsive insulins (smart insulins) a major goal. Our approach simplifies such design by exploiting an endogenous ‘smart’ switch in the liver, how the body naturally adjusts relative hormonal responses based on whether the blood glucose level is high or low: Too high, insulin wins; too low, glucagon wins!”
Michael Weiss was also supported by lab partner and colleague at Yale, Associate Professor Raimund Herzog, who was part of the team proposal and oversaw the animal testing.
Rachel Connor, Director of Research Partnerships at Breakthrough T1D UK, said:
“This new development in novel insulins research hold exciting promise for people with T1D. Avoiding low blood glucose is a constant balancing act for people with type 1 diabetes, as so many factors can combine to affect blood glucose levels. An insulin offering protection from hypoglycaemia could have a profound impact on the mental burden of living with T1D. With funding from the Type 1 Diabetes Grand Challenge, we’re excited to be driving innovations as fast as possible toward testing with people who live with T1D.”
Dr Elizabeth Robertson, Director of Research and Clinical at Diabetes UK, said:
“The Type 1 Diabetes Grand Challenge is committed to supporting innovation that meets the needs of people living with type 1 diabetes. These positive results are an exciting step towards next-generation insulins that could ease the burden of daily management with insulin therapy. We look forward to seeing this promising research advance into human studies and, ultimately, improve the lives of everyone who depends on insulin therapy.”
With new research such as this, there is a possibility to reduce the number of hypos, which would be safer for all people living with type 1 diabetes. This research is in its early stages, with many more steps to occur before it will be made available to the public. The eventual aim is to create two different types of insulin; a longer lasting version for use once a week, and a short acting version for use in insulin pumps.
