Insulin, which automatically turns on and off in response to blood sugar levels, has proven successful in reducing the risk of dangerously low blood sugar levels, or hypoglycemia, in animals. Researchers say the drug holds great promise for the tens of millions of insulin-requiring diabetics around the world.
Hypoglycemia, or low blood sugar, can be dangerous for diabetics. Because the brain relies on glucose to function properly, severe hypoglycemia can cause seizures and loss of consciousness. People who take insulin have questions like, “Did I take the right amount of insulin to cover this meal? Or is it too much?” It’s something I always worry about. or “How does the exercise I just did affect my blood sugar levels?”
Not long ago, New Atlas covered the development of nanotechnology to prevent potentially dangerous hypoglycemic events in diabetics. Now Novo Nordisk, the Denmark-based pharmaceutical giant responsible for manufacturing a range of insulins, has gone a step further and designed an insulin that switches on and off in response to blood sugar levels.
Designing insulin that can change its biological activity depending on blood sugar levels has been on researchers’ bucket lists since the 1970s. Sadly, despite years of hard work and attempts, nothing came of it.
“A better approach seems to be to give insulin itself glucose-responsive properties, allowing it to respond reversibly to glucose,” the researchers said. “Notably, because blood glucose levels fluctuate within a narrow range (approximately 2 to 20-30 mM (20-30 mmol/L or 360-540 mg/dL) in diabetic patients), the biological activity of insulin is There should be a fairly rapid change in glucose sensitivity achieved because of the effect it has on insulin.
To achieve this goal of glucose responsiveness, the researchers introduced an “on/off switch” into the insulin molecule. Under high glucose conditions, the modified insulin NNC2215 switches on, increasing insulin activity and absorbing excess blood sugar from the blood. When glucose levels drop, the switch closes and prevents glucose uptake.
They first tested NNC2215 in the lab to see how it reacted in the 3-20 mmol/L glucose range. They found that the binding affinity of the modified insulin to the insulin receptor increased 3.2-fold as blood sugar levels changed. Next, in rat and pig models, NNC2215 was found to be as effective as human insulin in lowering blood sugar levels, and its increased glucose sensitivity provided protection against hypoglycemia.
Although still in its early stages, the results of this study are promising. Novo Nordisk’s modified insulin has great potential to prevent rapid drops in blood sugar levels that are worrying and potentially dangerous for people with diabetes, especially those that occur during sleep.
In contrast to reasonable concerns about hypoglycemia, some people with diabetes develop a “hypoglycemic fear,” or a specific extreme fear, of blood sugar levels falling too low. People with diabetes who fear hypoglycemia may intentionally raise their blood sugar levels to avoid hypoglycemia, increasing their risk of diabetes-related complications and reducing their quality of life and mental well-being. Especially for these diabetics, glucose-responsive insulins like NNC2215 may help reduce fear.
“In conclusion, insulin conjugates with NNC2215-like properties may improve the treatment of diabetes by potentially lowering the risk of hypoglycemia and partially covering the need for fast-acting prandial insulin.” “It has the potential to do so,” the researchers said. “The combination of these two features should allow for more aggressive insulin titration without increasing the risk of hypoglycemia. This should reduce the short- and long-term risks and complications associated with diabetes. It could be improved.”
The study was published in the journal Nature.
Source: Novo Nordisk via Scimex
