ETH Zurich researchers from the Department of Biosystems Science and Engineering (D-BSSE) in Basel allow us an implantable device that precisely monitors acid build-up in the body for people with diabetes and produces insulin if acidosis turns into a risk.
Many human metabolic functions only run smoothly when the acid level in the body remains neutral and stable. For humans, normal blood pH values lie between 7.35 and seven.45. By way of comparison, an empty stomach is incredibly acidic, with a pH worth of 1.5.
Your body constantly monitors this narrow pH band and quickly restores the perfect pH values in the event of any deviations. It is because many proteins cease to operate properly if fluids in your body become even slightly more acidic. These proteins become unstable and alter their structure or interactions with other proteins, causing entire metabolic pathways to collapse.
People with type 1 diabetes are particularly at risk of high acid levels. Their health produce no insulin, the hormone that regulates blood sugar levels, so their cells cannot absorb any glucose in the blood and also have to tap into another power source: fat reserves. By doing this, the liver produces beta-hydroxybutyrate, an acid which supplies the muscles and brain with energy through the bloodstream. When the body is constantly on the use fat reserves for energy, however, this produces a lot acid the blood’s pH value plummets as the sugar molecules circulate within the blood unused. When the lack of insulin is not noticed or treated in time, individuals with type 1 diabetes can die from ketoacidosis C metabolic shock caused by an excess of beta-hydroxybutyrate.
A group of bioengineers from ETH Zurich’s Department of Biosystems Science and Engineering (D-BSSE) in Basel have finally developed a new implantable molecular device composed of two modules: a sensor that constantly measures blood pH and a gene feedback mechanism that creates the necessary quantity of insulin. They constructed both modules from biological components, for example various genes and proteins, and incorporated them into cultivated renal cells. The researchers then embedded millions of these customized cells in capsules which can be used as implants in the body.
The heart from the implantable molecular device is the pH sensor, which measures the blood’s precise acidity and reacts sensitively to minor deviations in the ideal pH value. When the pH values falls below 7.35, the sensor transmits a signal to trigger the production of insulin. Such a low pH value is specific for your body: although blood pH also drops due to excessive drinking or exercise due to the overacidification of the muscles, it doesn’t fall below 7.35. The hormone insulin ensures that the standard cells in the body absorb glucose again and switch from fat to sugar his or her power source for metabolism, and also the pH value rises again consequently. Once blood pH returns towards the ideal range, the sensor turns itself off and also the reprogrammed cells stop producing insulin.
The researchers have previously tested their invention on mice with type 1 diabetes and related acidosis. The outcomes look promising: mice with the capsules implanted produced the amount of insulin appropriate for their individual acid measurements. The hormone level within the blood was similar to those of healthy mice that regulated their levels of insulin naturally. The implant also compensated for larger deviations in blood sugar.
“Applications for humans are conceivable based on this prototype, but they are not yet been developed,” says Martin Fussenegger. “We wanted to create a prototype first to see whether molecular prostheses could even be employed for such fine alterations in metabolic processes,” he says. Preparing for example this for the market, however, is beyond the scope of his institute’s staff and savings, Fussenegger says, and would thus have to be pursued in collaboration with an industrial partner.
Researchers in Fussenegger’s group have already made headlines several times concentrating on the same synthetic networks. For example, they developed an implant with genes that may be activated with blue light, thereby producing GLP-1, which regulates insulin production. They also come up with a network that eliminates metabolic syndrome, a procedure set in motion by an authorized blood-pressure medicine. Many of these networks respond to an indication and produce a hormonally active substance. The special aspect of the new feedback mechanism, however, would be that the body itself creates the signal, which is then detected by a sensor that creates a fine-tuned therapeutic reaction.
Three groups from the D-BSSE done the current project. Fussenegger’s group developed the genetic network; Professor of Biosystems Engineering Andreas Hierlemann and his team tested the acidity sensor using microfluidic platforms; and J?rg Stelling, a professor of computational systems biology, modelled it in order to estimate the dynamics of the insulin production.
