The new modified insulin itself senses when to lower blood glucose levels.
The pancreas regulates blood sugar levels using the hormone insulin – it causes body tissues to absorb glucose. The pancreas learns about when and how much insulin is needed thanks to various physiological signals, and its insulin, having done its job, is broken down quite quickly. That is, in healthy people it does not happen that excess insulin floats in the blood. The situation is different for diabetic patients. In both type 1 and type 2 diabetes, the pancreas produces too little insulin, if any at all (although the reasons for this are different for both diabetes). Patients begin to experience chronic hyperglycemia, that is, elevated blood sugar levels, which is fraught with neurological pathologies, kidney diseases and many other troubles; acute hyperglycemia leads to confusion and coma.
To prevent this from happening, you need to regularly inject yourself with insulin – but inject it under the skin, from where it takes a long time and gradually enters the blood; Such insulin is broken down significantly slower than insulin from the pancreas. Moreover, some insulin preparations are specially made to last longer. But with long-acting insulin, another problem arises. A person may be late with lunch, or, for example, he will have some kind of physical activity, and then, against the background of “slow” insulin, the blood sugar level will drop below normal. Hypoglycemia will occur, which is no better than hyperglycemia – with it, too, everything can end in loss of consciousness and coma.
It would be convenient if the administered insulin sensed when it was necessary and when it was not necessary to stimulate the absorption of glucose. They have been trying to create such insulin for quite some time, using a variety of tricks. Employees of the pharmaceutical company Novo Nordisk achieved some success here – in an article in Nature they describe a modified insulin that turns on only when the surrounding glucose level is elevated. A glucose-like molecule was attached to the insulin polypeptide chain at one end, and another molecule was attached to the other end, which should bind it. While there is little free glucose around, the glucose-like molecule at one end is connected to the molecule that binds it at the other end – both ends of the modified insulin are connected, and in this form it is inactive. That is, insulin modifications work like a switch. If the level of glucose in the environment increases, it displaces the glucose-like molecule from the switch, the molecular ring is disconnected, and insulin is now able to interact with its receptors. And, importantly, when the glucose level drops, insulin will turn off until it rises again.
Both modifications had to be made so that they did not interfere with the insulin itself; and the molecule that was supposed to bind to glucose at the end of insulin had to be made so that it would disconnect the ring (and activate insulin) only at a certain concentration of glucose. The design was tested first on pure insulin receptors, and then on a cell culture: the modified insulin bound to its receptor and triggered the corresponding molecular processes in the cells, and the cellular effect depended on the glucose concentration. Switch insulin was also tested in mice and pigs. In mice, it lowered the blood sugar level in proportion to the level of this sugar (that is, if there was not very much glucose, then it did not lower it much), and in pigs it did not experience hypoglycemia, unlike those cases when they were injected with regular insulin drug.
However, the new insulin has now been tested over a relatively wide range of glucose concentrations. In humans, normal blood sugar levels and their increase after meals are fairly close numbers, and the question arises whether modified insulin can be adjusted to the desired sensitivity. Another question is related to its lifespan: in experiments on mice and pigs, it was still destroyed faster than it should have been, and if we talk about using it in the clinic, the stability of the molecule needs to be somehow increased. Further research will show whether the new insulin can be further improved.
Source: www.nkj.ru
