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'Smart' insulin beats the regular kind in diabetic mice

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One step closer to controlling insulin's side-effects

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A lab-made insulin molecule can sense and regulate blood sugar levels in a mouse model of diabetes, according to a study published in Proceedings of the National Academy of Sciences today. Even though the study took place in mice, the finding is pretty significant; it's the first time researchers have shown that a tweaked version of insulin can regulate itself in a living animal. If the finding translates to humans, it could lower the amount of insulin injections required by people with diabetes and prevent some of the dangerous complications that injecting too much insulin can cause.

"Right now, all of the insulin that a patient takes is ‘dumb.'"

Over 29 million people in the US suffer from some form diabetes, a condition in which people either lack the insulin necessary to regulate blood sugar, produce too little insulin, or make  ineffective insulin. People with diabetes regulate their blood sugar levels by injecting insulin, which allows the sugar in the blood to be absorbed into skeletal muscles and fat tissues. But this means continuous monitoring of blood sugar levels, and adherence to a specific diet. And unfortunately, even when those guidelines are followed precisely, patients can still experience serious complications.

"Right now, all of the insulin that a patient takes is ‘dumb,’ in a way," says Daniel Anderson, a molecular geneticist at the Harvard–MIT Division of Health Sciences and Technology and a co-author of the study. The molecules do their job whether blood sugar is high or low. That means that insulin-injecting patients run the risk of hypoglycemia if their blood sugar is low when the insulin is in their system — and that means serious consequences, like passing out, seizures, and rapid heartbeats. Almost 100,000 people visit the ER for insulin-related hypoglycemia yearly.

"Insulin is a very important drug for diabetics, but it’s also fickle in some ways," says Anderson. It works great in healthy people because the pancreas can regulate sugar levels. "But for patents that are sick, it’s very hard to get the right amount." That’s why creating a synthetic form of insulin that’s smarter than what humans produce naturally would be such a huge breakthrough. Doing that would "get us one step closer to having insulin that behaves the way it’s supposed to in the body with a normal, healthy pancreas."

it restored normal blood glucose levels more quickly than regular insulin

To do this, Anderson and his team chemically modified insulin by introducing an acid into the molecule. That modification helps insulin bind to sugar in the blood stream — something normal insulin doesn’t do — and regulate the presence of sugar in a diabetic mouse’s blood. "We don’t full understand how these things work," Anderson says, but the basic idea is to have insulin that can affect the patient depending on how much sugar is present around it. Binding to sugar in the bloodstream seems to help the insulin work with a lower likelihood of hypoglycemia, he says.

Despite not completely understanding how the modified insulin works, the researchers were able to make molecules that can restore normal blood glucose levels in mice who had been given a "simulated meal" — an injection of glucose — more quickly than regular insulin or a long-acting form of insulin, both commonly used by people with diabetes. The best performing lab-made insulin derivative was able to respond to multiple glucose injections over a 13-hour period.

it's not perfect

The study was only done on mice, so it will take quite a while before a modified form of insulin makes it to market, Anderson says. "It’s all speculation, but you could envision a [human] clinical trial in three or four years, assuming a bunch of other things work out," he says. "And obviously the clinical approval process is a big long thing," so a modified form wouldn’t be available for consumers for another few years after that. In the meantime, the researchers plan to make the modified insulin more effective. Right now it performs better than conventional forms, Anderson says, but it’s not perfect. "We would like to make it better, so that if a patient got 10 times more insulin [than they need], they wouldn't get a hypoglycemic response." They also have to keep studying it in mice to make sure it’s safe before moving onto humans. "That said, it's a very interesting molecule," he says, that "diabetes nerds" will appreciate.