An artificial pancreas that supplies two hormones

Against type I diabetes
An artificial pancreas that supplies two hormones: insulin and glucagon
The experts saw that the same insulin acts differently in each patient
There are several technical limitations that prevent their immediate arrival from the patient
Cell regeneration and islet transplantation, other alternatives
Updated Thursday 04/15/2010 05:04 (CET)
María Sainz
Madrid.- By excess or by default, sugar can become a poison for diabetic people.In the search for a perfect artificial pancreas, which supplants the physiological abnormalities, a group of American experts has found two essential keys to this device.It should be taken into account that insulin behaves differently in each patient and that, in addition to administering this hormone, another, glucagon, involved in controlling low glucose levels.

Until now, the closest to artificial pancreas are the continuous insulin infusion pumps, connected to the patient subcutaneously, and that complement each other with a glucose sensor that measures sugar levels.At the moment, no system works completely autonomously and, often, the appearance of hypoglycemia (sugar descents) cannot be avoided.

Aware of this void, the researchers at the University of Boston and the General Hospital of Massachusetts (USA) launched an essay to prove the effectiveness of a system that would administer not only insulin, when glucose figures are high, but also glucagon, a hormone that avoids the opposite phenomenon, the decrease in sugar.Its results are collected in 'Science Translational Medicine'.

Firas H. El-Khatib and his team tested, for the first time, their system in humans (they had done so in pigs): 11 people with type I diabetes analyzed for periods of 27 hours in a row.To treat them, they applied a new mathematical algorithm that translates sugar measurements into insulin and/or glucagon administration guidelines.

"The pancreas of people with type I diabetes does not have beta cells, which produce insulin, because their immune system has destroyed them. Alpha cells, in charge of releasing glucagon, are present but do not work properly. Therefore, they areUpon suffering both a sugar and hypoglycemia rise, "explains Steven Russell, one of the authors, Elmundo.es.

Different effects on each patient
His scientific work not only stands out for the 'bihormonal' use but also because he demonstrates that each patient absorbs insulin differently.In fact, the first time experts tested this artificial pancreas, five of the 11 participants experienced hypoglycemia.

"It is normal for insulin to reach its greatest presence in the blood between 30 and 90 minutes of its administration. However, we saw that these times varied a lot. For example, a patient presented that maximum peak at 191 minutes," he addsRussell.

Therefore, in a second phase, a series of parameters were modified based on this different hormonal absorption.As a result, drastic sugar falls and increases were avoided in all participants.

Limitations for clinical application
Without subtracting importance to these findings - the glucagon had never been used in this way or such a specific algorithm had been designed - an article, published in the same magazine, highlights some of its possible limitations.

Its signatories, Larry Brown and Elazer R. Edelman, comment that different hormones come together in the pancreas, not only the two mentioned, which should also be taken into account.And they clarify that managing glucagon can be a challenge since it is a very unstable substance.

When taking it to clinical practice, the editorialIt also refers to the chosen way to control sugar levels.In the El-Khatib essay, these were measured every five minutes and directly by vein;Something that does not seem very viable when developing a portable device.

In this sense, Alfonso Calle, head of the Endocrinology and Nutrition Service of the Madrid Clinical Hospital, is expressed.Recognize the value of the new essay, especially the designed algorithm, but clarifies that the system is still far from reaching patients.

"The insulin pumps currently measure glucose in the interstitial tissue, clicking the abdomen, and the figure they obtain has 20 minutes of delay. It shows the presence of sugar at that time, not of that moment. In the vein or vein orFor the capillary fabric (on the finger) a real result is achieved, but they are not feasible or so comfortable methods.

As he adds, it would also be necessary to replicate this essay but with patients who are not in an 'ideal' situation.That is, without being hospitalized and without controlling your food or being able to exercise.These two factors - food and physical activity - are essential for the balance of this disorder.

Alternatives to artificial pancreas
Although research in the artificial pancreas area is highly developed, it is not the only open route around the treatment of type I diabetes. In fact, Brown and Edelman comment in their opinion article the important role they could play, in aFuture, "cell therapies", such as the use of undifferentiated stem cells, both embryonic and adult, to produce new transplantable beta cells to patients.

Another option is the usual pancreatic islet transplants (where the endocrine cells of the pancreas are found).These come from donors and are introduced with a catheter through the portal vein and are implanted in the liver.

The liver islet transplantation, however, is not effective in the medium term, as Pedro Herrera, professor of the Faculty of Medicine of the University of Geneva (Switzerland)."It is a transplant and, as such, it needs patients to receive immunosuppressive therapy that, as has been known recently, also ends up destroying beta cells that have been implanted."

Precisely, Herrera is the main author of a study published last week in 'Nature' and in which another of the new keys to overcome type I diabetes is treated: regeneration.

"We wanted to know if it is possible that an adult pancreas in which all beta cells have been destroyed, as is the case of type I diabetic patients, can regenerate new beta cells [...] for a long time doctors have known that there areA small number of beta cells persist in people who have been diabetic for years;

This essay, carried out in adult transgenic mice in which the elimination of cited cells can be selectively induced, and that they also do not have the immune problem, it suggests that the second option is correct.The pancreas of adult mice can regenerate up to 10% of the mass of beta cells present in a healthy pancreas.

The second surprising observation made by the team of this Spanish researcher at the University of Geneva is that the main source of regeneration of these beta cells is precisely alpha cells (which release glucagon).

Indeed, the researchers observed that the massive loss of beta cells induces conversion ("reprogramming") of a part of alpha cells in insulin manufacturers.And that this happensspontaneous way, without the need to induce any process.