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Living with type 1 diabetes is an act of juggling diet, exercise, and insulin therapy to keep blood sugar levels normal. While there are plenty of solutions to try to make life easier for people with diabetes, a promising new approach focuses on insulin itself.
Michael Weiss, a biochemist at Indiana University School of Medicine in the United States, and his colleagues returned to the drawing board on the insulin molecule, fine-tuning the structure to respond to the presence of a simple carbohydrate, with the aim of reconnecting the activation of insulin with internal blood sugar levels again.
Their modification focuses on a feature already built into the shape of the molecule – a protective “hinge” that allows the protein to function when open, otherwise keeping it stable when closed.
(IU School of Medicine, 2021)
A new design means that the insulin molecule only opens in the presence of a “key”, such as a single sugar molecule.
The experiments carried out by Weiss and his team used fructose, a carbohydrate, showing that it was possible to manipulate insulin so that it only activated a sample of cells derived from the liver when it was “activated. »By the presence of a certain amount of sugar.
More a proof of concept than a proven therapy, the idea would theoretically work the same way for an insulin-like “hinge” to activate instead in the presence of glucose. The result paves the way for a way to smooth out much of the guesswork in the treatment of diabetes.
“The promise of this type of ‘smart’ insulin is that it would transform diabetes care, so people don’t have to worry anymore,” Weiss explains.
Type 1 diabetes is an autoimmune disease that affects about 15 in 100,000 people worldwide. This is because the body’s immune system destroys the cells in the pancreas responsible for measuring precise amounts of the hormone insulin based on the levels of glucose floating in the blood supply.
Without controlled amounts of insulin delivered to the body at the right time, the doors that would normally channel glucose into cells remain firmly locked, cutting off fuel to energy-consuming tissues and organs when they need it most.
For people with diabetes in centuries past, this tragically would have meant premature death. Fortunately, the fates of millions of people changed with the discovery that insulin could be purified and injected artificially, grossly doing the pancreas’ job on its behalf.
It is an effective remedy, but not without many challenges. The body’s hunger for glucose is far from predictable, causing levels to go up and down seemingly on a whim.
Without enough insulin, blood sugar can stay high in a hyperglycemic state, causing a litany of symptoms ranging from excessive thirst to headaches, blurred vision and fatigue.
Overload your body with insulin and the cells quickly engulf the blood glucose supply, instead leading to a state of hypoglycemia. In mild forms, this low sugar level leads to excessive sweating, confusion, tremors, and irritability. In severe forms, hypoglycemia increases the risk of seizures, and sometimes even leads to death.
No matter which direction you take, when there is not enough glucose, the body turns to fat for energy, producing ketones as waste. If these build up in large enough amounts, the result is a potentially dangerous condition called ketoacidosis.
Advances in knowledge and technology have certainly helped individuals manage their blood sugar levels to avoid tragic results. But turning the insulin molecule into a biochemical sensor itself could weave a fail-safe mechanism that renders the hormone ineffective when blood sugar drops below a certain point.
“The reason why glucose-sensitive insulin is important is that the biggest obstacle to the effective use of insulin, especially in type 1 diabetes, is fear of the consequences of too low blood sugar,” explains Weiss.
The concept is being explored by other researchers. Last year, a team of scientists from the University of Copenhagen and biotech company Gubra found success in a similar approach, creating a form of insulin with an attached group that separated in the presence of glucose. to make the molecule functional.
It has been shown to work in rats, yet another potential automated insulin that may one day be incorporated into treatments.
There’s got to be a lot going on by then. While effective in theory, the modified hormone should be smart enough to recognize a very specific glucose threshold.
2021 marks the centenary of the discovery of insulin. One hundred years from now, those facing the challenges of type 1 diabetes may look back on another century, when insulin got a makeover.
This research was published in PNAS.
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