It is known that at present more than 400 million people around the world suffer from diabetes. Treatment for type 1 diabetes mellitus and advanced type 2 diabetes mellitus is multiple daily injections or continuous infusion of exogenous insulin.
However, realizing the benefits of insulin therapy is not always possible, given the risk of hypoglycemia due to overdose of the drug, which can lead to seizures, coma and death.
Find out in our article on estet-portal.com what are the scientific discoveries in the field of glycemic control in diabetes mellitus 1st and 2nd type.
Development of a new insulin delivery system
Given the disadvantages of parenteral insulin administration, numerous studies have focused on the development of intelligent insulin delivery systems that can mimic glucose-dependent dynamic secretion by β-cells, thereby leveling hyperglycemia and reducing the risk of insulin hypoglycemia associated with miscalculation of the dose of exogenous insulin.
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In this perspective, chemically controlled artificial closed insulin delivery systems based on phenylboronic acid, glucose-binding protein and glucose oxidase are being intensively studied. However, strategies for precise control and regulation of blood glucose levels, combined with a low risk of hypoglycemia, remain poorly understood.
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Research on new glucose transporters
In a new study by a team of scientists at the University of California, Los Angeles, USA, a modified model of insulin was proposed based on a simple conjugation of insulin with a reverse glucose transporter inhibitor (Glut).
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Transmembrane Protein Glut
It is known that Glut belongs to the family of transmembrane proteins that facilitate the transport of glucose across plasma membranes. At the same time, various compounds are able to competitively block the glucose transport activity of Glut.
In the presence of a Glut inhibitor, the insulin analog is able to form a feedback and dynamic relationship with the Glut receptors of cell membranes.
In this case, the degree of coupling will be modulated depending on the concentration of glucose, which thus forms the sensitivity of the insulin molecule to glucose. After administration, by subcutaneous injection, of the developed insulin analog, it binds to insulin receptors as well as endogenous Glut, thus creating an in situ generated reservoir of the complex based on the insulin analog and Glut.
After an increase in glucose levels, for example, against the background of taking the next portion of food, there is a dissociation of the complex, which includes an insulin analogue and Glut. This results in the release of Glut on the plasma membranes and the insulin analog compound into the interstitial space and blood plasma.
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Clinical trials of insulin analogues
Further, the free insulin analogue can bind to insulin receptors, causing translocation of Glut4 to cell membranes and improving glucose clearance relative to muscle and adipose tissue. Meanwhile, Glut, which was previously unavailable to glucose, as part of the insulin analogue-glut protein complex, is able to increase blood glucose clearance.
However, at excessive doses, the insulin analogue induces overexpression of Glut on plasma membranes, subsequently causing glucose uptake into cells, potentially contributing to the development of hypoglycemia.
The formation of glucose-sensitive complexes based on the insulin analog and the Glut protein can suppress the efficiency of Glut's glucose transport function, to a certain extent leveling the risks of hypoglycemia.
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Thus, in preclinical experiments on laboratory animals with modeled type 1 diabetes, researchers have demonstrated the ability of the above insulin conjugate to regulate blood glucose levels within the physiological range, while reducing the risk of developing a hypoglycemic state. The treatment model is now outlined and is being evaluated for further clinical trials and, if successful, − implementation in the strategy of daily therapy of real patients with diabetes.
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