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Magnetic microparticles to stimulate insulin secretion

An innovative diabetes treatment solution has been developed by IRIG researchers. Mechanical stimulation of pancreatic beta cells plasma membrane, via the vibration of magnetic microparticles, was shown to trigger insulin secretion.

Published on 6 December 2022
In 2021, diabetes is a disease that affects approximately 537 million adults, according to the International Diabetes Federation. There are two types of diabetes that lead to hyperglycemia, i.e. too much glucose in the blood. The amount of blood glucose is regulated by the hormone insulin which is secreted by the pancreas. Type 1 diabetes results from a lack of insulin secretion while type 2 diabetes is due to a misuse of insulin by the body's cells. Patients with diabetes, typically monitor their blood glucose levels several times a day and then inject appropriate doses of insulin subcutaneously. This blood glucose control is for most patients, done manually. More integrated solutions exist, but several technical problems persist and the technology is still invasive. The optimal medical device will include a blood sugar sensor able to monitor continuously, an algorithm to calculate the appropriate insulin dose, and an insulin pump. Regarding diabetes treatment, other lines of research can be considered, such as the development of artificial pancreas or the stimulation of the deficient pancreas in diabetic patients.

In this context, researchers from the IRIG are studying how to stimulate insulin secretion by a failing pancreas. They use the vibration of magnetic microparticles deposited on the surface of pancreatic beta cells. Researchers had already used these particles to induce the death of cancer cells by apoptosis. These are microdisks (diameter: 1.3 µm; thickness: 60 nm, figure A), composed of iron and nickel, and which can be coated on both sides with a layer of gold (Au/Fe20Ni80/Au). When they are deposited on INS-1E (Figure C) pancreatic beta cells and when the whole assembly is subjected to a low frequency magnetic field, the vibration of the particles stimulates the cell surface, which results in insulin secretion. The amount of insulin produced depends on the concentration of particles applied to the cell surface (10 to 50 µg/mL), the frequency of the magnetic field (10 to 40 Hz) and the duration of the stimulation (5 to 30 minutes).

Under optimal conditions, the amount of insulin secreted is close to that observed when the cells are stimulated via an effective concentration of glucose. This mechano-stimulation is not deleterious to the cells and does not lead to apoptosis. However, these magnetic microparticles are internalized by the cells. To overcome this effect and to guarantee the safety of the device, the researchers incorporated the magnetic microparticles into a polydimethylsiloxane (PDMS) polymer film (Figure B). The new device avoids internalization of the particles and leads to insulin secretion by the cells (Figure D).

Thus, the mechano-stimulation of the surface of pancreatic beta cells, via the vibration of magnetic particles isolated or included in a polymer film, leads to insulin secretion and could eventually become one of the components of an artificial pancreas. It is also possible to imagine the implantation of magnetic particles in the deficient pancreas of diabetic patients.

A) SEM image of the Fe20Ni80 magnetic particles used for magneto-elastic membrane fabrication
B) Fabrication of Fe20Ni80 magnetic particle-doped PDMS membranes, forming a well in which cells can be grown
C) INS-1E pancreatic cells exposed to (agglomerated) microparticles (magnification × 200)
D) Magnetic field source device to stimulate insulin secretion: image of the system with a 12-well plate placed above spinning disk. The spinning disk containing magnets is mounted on a speed controlled DC motor/gearbox that is linked to an optical breadboard.
Credit CEA​

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