Have combined incompatible
A research team from Stanford University has found a way to increase the effectiveness of insulin injections, which people with diabetes have to receive regularly to regulate blood glucose levels. This discovery will allow patients to get an injection containing the hormones insulin and amylin.
Amylin is produced together with insulin by beta cells of the pancreas in a ratio of 1:100, together they regulate the level of glucose in the blood after eating. The combined action of these proteins is more natural and effective than insulin alone.
A synthetic analog of amylin, pramlintide, is already commercially available, but it is estimated that less than one percent of patients with insulin-dependent diabetes receive this additional treatment. The fact is that the two hormones that work together in the body are too unstable in vitro to coexist in one bottle. And every time after an injection of insulin, patients often do not want to take another injection.
A new form with two hormones in one syringe or in an insulin pump would allow them to be injected into the body simultaneously.
Protective coating
The new technique includes a protective shell that covers the molecules of insulin and pramlintide, allowing them to coexist in one bottle.
This shell is destroyed in the blood, and the two hormones work together, simulating the functioning in the body of healthy people.
To make it possible to combine insulin and pramlintide in one syringe, researchers have developed a molecular shell made of polyethylene glycol (PEG), a non–toxic chemical widely used in the manufacture of medicines and cosmetics. A group of researchers used a new type of PEG with a molecular "Velcro" at the end, called cucurbituril-PEG. The ability to adhere allows PEG to reversibly bind to both insulin and pramlintide separately, protecting the unstable parts of each molecule from destruction. However, once injected into the body, the drugs detach from the PEG and can act unhindered.
In laboratory tests, the researchers heated packaged and unprotected insulin to normal body temperature and shook it – a process known as stress aging. This was done to assess the stability of the drug. They found that the unprotected insulin in the test tube was stable for just 10 hours, while PEG insulin remained fully active after 100 hours. Without coating, two drugs in one bottle were destroyed in just 3 hours. The combination of PEG-insulin and PEG-pramlintide remained stable for at least 100 hours, which is a sufficiently long shelf life for administration with an insulin pump.
In tests on pigs, the researchers observed a high activity of the drug with two drugs, which triggered processes occurring in a healthy body, including almost complete suppression of the action of glucagon.
Imitating the body
The coating of insulin and pramlintide molecules with a protective shell will allow patients with diabetes a convenient way to simulate their natural secretion in the human body. Insulin improves the absorption of sugar by cells, removing it from the bloodstream. Pramlintide, firstly, does not allow the hormone glucagon to signal the release of additional carbohydrates that are stored in the liver. Secondly, while eating, it causes a feeling of satiety, reducing food intake. Thirdly, it slows down the absorption of food by the body, reducing the characteristic surge of glucose in the blood after eating.
The authors write that the few patients who currently receive pramlintide after each insulin injection feel the benefits of such a therapy regimen. The available clinical data show that the combination of drugs helps them to normalize excess weight and better control blood glucose levels.
Improved diabetes treatment will help reduce the risk of serious complications such as kidney failure, blindness, cardiovascular disease and amputation, which threaten anyone with diabetes.
Next steps
Since both drugs have already been approved for sale, and the composition of the dual drug has been tested on the best preclinical model, the group must now demonstrate that their technique is non-toxic to humans, and then begin clinical trials.
The authors have applied for a patent for the technology.
Article by C.L.Maikawa et al. A co-formulation of supramolecularly stabilized insulin and pramlintide enhances mealtime glucagon suppression in diabetic pigs is published in the journal Nature Biomedical Engineering.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Stanford University: An experimental new injection might help diabetes.