A sensitive acidity sensor that initiates insulin production

A team of bioengineers has now succeeded in developing a new implant which is a molecular device and which consists of two components: a sensor that continuously measures the level of acidity (pH) in the blood and a gene-based feedback mechanism that leads to the creation of exactly the required amount of the insulin protein.

[Translation by Dr. Nachmani Moshe]
A team of bioengineers has now succeeded in developing a new implant which is a molecular device and which consists of two components: a sensor that continuously measures the level of acidity (pH) in the blood and a gene-based feedback mechanism that leads to the creation of exactly the required amount of the insulin protein.

A team of bioengineers has now succeeded in developing a new implant which is a molecular device and which consists of two components: a sensor that continuously measures the level of acidity (pH) in the blood and a gene-based feedback mechanism that leads to the creation of exactly the required amount of the insulin protein. Many metabolic functions will function properly only if the acidity level in the body remains neutral and stable. For humans, a normal state of blood acidity is in the range of 7.45-7.35. Compared to this, an empty stomach is extremely acidic and has an acidity level of 1.5.

The body continuously monitors this narrow pH range and quickly returns the ideal values ​​in case of deviations from the healthy range. This, in light of the fact that many proteins stop functioning properly if the fluids in the body become even slightly more acidic. The proteins lose their stability, their structure changes, their interactions with other proteins change and all this causes the metabolic pathways to go wrong.

People with type 1 diabetes are especially at risk in a state of high acidity. In this situation, their body does not produce insulin, which is the hormone that regulates blood sugar levels, and therefore their cells are unable to absorb sugar from the blood and are forced to get their energy from another source: fat reserves. During this phase, the liver produces the substance beta-hydroxybutyrate, an acid that supplies energy to muscles and brain cells through the bloodstream. However, if the body continues to use the fat reserves to create energy, such a large amount of acid is created that the acidity level of the blood drops while the sugar molecules in the bloodstream remain unused. If the lack of insulin is not noticed or treated, the patients with type 1 diabetes eventually get rid of a condition known as ketoacidosis [ketone bodies and acid in the blood] - a metabolic shock resulting from an excess of the substance beta-hydroxybutyrate.

A team of bioengineers from the Department of Biosystems Sciences and Engineering from the Zurich Institute of Technology in Basel (ETH) has now developed a new implant which is a molecular device and which consists of two components: a sensor that continuously measures the level of acidity (pH) in the blood and a gene-based feedback mechanism that results in the creation of the required amount Just like the protein insulin. The researchers combined biological components in their system, such as various genes and proteins, while assimilating them into kidney cells. In the next step, the researchers implanted millions of adapted cells of this type inside capsules that can be used as implants inside the body. The core of the implant device is an acidity sensor, which regularly measures the exact acidity level of the blood and reacts with high sensitivity to tiny deviations from the ideal acidity values. If the value falls below 7.35, the sensor sends a signal that initiates insulin production. Such a low acidity value is specific to type 1 diabetics. Although a drop in the acidity level also occurs due to increased use of alcohol and physical exercise due to excessive acidity of the muscles, the values ​​in these cases do not decrease from a value of 7.35.

The hormone insulin ensures that the cells in the body absorb the sugar again and transfers the source of energy used by the body from fat reserves to sugar, as a result of which the acidity value rises again to its normal value. As soon as the acidity level of the blood returns to its ideal value, the sensor stops working and the programmed cells stop producing insulin.

The researchers have already had time to test their invention on mice with type 1 diabetes and the acidosis associated with this condition. The results look promising: the mice in which the innovative capsules were implanted produced the amount of insulin required for the healthy ranges for them. The level of the hormone in the blood was equal to that of healthy mice that manage to regulate their insulin levels naturally. The implants were also able to compensate for large deviations in the blood sugar level.

"Human-adapted applications based on this prototype are certainly conceivable, but have not yet been developed," says one of the researchers. "First of all, we wanted to develop a prototype in order to see if molecular artificial organs can be used for such sensitive adaptations in metabolic processes," he adds and says. At the same time, the development of this kind of product and its commercial marketing is beyond the scope of the team of researchers and the financial resources available to them, says the chief researcher, and he hopes to create collaborations with a partner from the industrial sector.

Some scientists from this research team have already made headlines several times in the past as part of their development of similar synthetic networks. For example, they developed a gene-based implant capable of being activated with blue light radiation, and in the process produce GLP-1 [Glucagon-like peptide-1], a substance that regulates insulin production in the body. They also managed to integrate a network that prevents the metabolic syndrome, a process activated by a drug to lower blood pressure. All these networks responded to the signal by producing the hormonally active substance. However, the special feature of the new feedback mechanism is that the body itself produces the signal, which in the next step is detected by the sensor that generates an adapted medical treatment response.

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