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Imagine this. Insulin responds to changes in blood sugar levels. Insulin works when it's needed and stops when it's not needed.
Pharmaceutical companies have been working on developing so-called “smart insulins” for decades. Smart insulin could allow diabetics to more aggressively target normal blood sugar levels. It reduces the risk of both hypo and hyperglycemia and may lead to improved health in both the short and long term.
“Developing a ‘smart’ insulin requires a lot of chemistry,” he says. Dr. Matthias von Hellasscientific director. diabetes research institute He is also Vice President and Senior Medical Officer of Novo Nordisk.
Today, this innovation is still far from human clinical trials, much less on the shelves of your local pharmacy, but it has been a breakthrough. Dr. von Hellas spoke to Diabetes Daily about Novo Nordisk's recent successful original experiment. glucose responsive insulin. Here, we take a closer look at researchers' progress and why it's so complicated.
Smart insulin must be perfect
“Developing a glucose-responsive insulin means we need to build a molecule that activates when it recognizes glucose,” says von Heras, who is not directly involved in Novo Nordisk's smart insulin research. says.
“I know Type 1 people are thinking things like:” [smart insulin] It’s like a vacation,” von Heras says. However, chemically speaking, many things are required of molecules. Constructing a type of molecule that activates only when it recognizes glucose is a challenge. ”
Von Hellas listed some of the most significant obstacles.
Smart insulin requires extreme precision. Glucose-responsive insulin must be highly accurate to ensure safety. You need to know exactly when and how much insulin to release. You also need to know when to do it. Stop To release insulin. “What will happen if I eat it and activate it?” all How much glucose-sensing insulin and what is the right amount? Again, this is a huge question! ” says von Heras.
Smart insulin carries the risk of cross-reactivity. There are other substances similar to glucose in the body, von Heras explains. “There is a huge safety risk when these glucose-sensing molecules cross with other drugs and hormones that can be confused with glucose,” von Heras said. It says extensive research is needed to address it.
Diabetes is not just about insulin. Within 20 seconds of eating, the islet cells of your pancreas begin communicating with various cells in your body. This includes beta cells, which produce insulin, but there are many other cells and hormones that play important roles in how the body manages food.
Smart insulin must be perfect: Imagine a day's worth of “smart insulin” sitting in your body, waiting to be activated by a rise in blood sugar levels. What would happen if it suddenly became active for no reason? Like an insulin pump releasing 50 units of insulin into the body all at once. This can easily become fatal. For glucose-sensing insulin to be truly safe for human use, it must be essentially perfect. It is not easily confused or blocked by other aspects of the body.
new molecule
Although it's a big challenge, researchers have made important progress.
Scientists at Novo Nordisk have developed a molecule they named NNC2215. This molecule essentially has a “switch” that responds to rising glucose levels in the bloodstream, allowing insulin to become more or less active. When blood sugar levels rise sufficiently, insulin activity increases. When blood sugar levels drop, the molecules slow down and shut off, preventing glucose from being taken up.
The first successful trial of NNC2215 was recently conducted. A team led by researcher Rita Slaby tested the molecule's effectiveness using rat and pig models. When blood sugar levels rise from 50 mg/dL to 360 mg/dL, glucose-responsive insulin becomes more responsive and takes in more glucose.
The results showed that the new insulin was as effective as human insulin in lowering blood sugar levels. And as expected, exposure to hypoglycemia significantly reduced insulin activity.
“Chemistry is progressing in amazing ways,” von Heras says. “I'm amazed that it's possible! When this topic first came up 20 years ago, I thought, 'No one can build something that works like that.' It’s impossible.”
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NNC2215 is not yet ready for human use, and even if it does get FDA approval, it will be years away. But its success led von Herert to change his mind about the possibility of glucose-responsive insulin.
“When I first saw these advances and chemical reactions, I thought, 'Wow, this is amazing,' but I'm still very cautious about saying it exists. We're making progress, but we have a long way to go.” .”
Von Hellas also said that this first type of glucose-responsive insulin will not be the magical solution to the challenge of feeding food that many type 1 patients hope. . “The first versions of these insulins were to prevent hypoglycemia. I tempered my expectations that they would be fast-acting insulins that could respond to food,” von Heras says. “I don't want to disappoint anyone, but I think it's going to take more time.”
The challenge, he said, lies in the exacting precision with which such drugs need to be proven to be reasonably safe.
“It has to operate with very high specificity and sensitivity. It has to be completely fail-safe. Like a gas line, it can't leak. It has to be very accurate.”
Regardless of the long road ahead, von Herert said progress is important and worth celebrating.
“At the Diabetes Institute, we celebrate every small victory, but we should also celebrate these advances and small wins in glucose-sensing insulin,” he added. “But this is the foundation of a path that requires quite a few small victories.”
While Von Hellas is optimistic and excited about the future of “smart” insulin, she knows her perspective is not the same as someone who lives with the daily burden of type 1 diabetes. .
“I'm a glass half-full person, but that's easy to say when you're not living with T1D yourself,” von Heras says. “But patients need to understand this research and why it's so difficult. Ten years ago we never thought something like this would be possible, but we've come a long way. I did.”
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