Optogenetics against diabetes
Smart watches and optogenetics normalized glucose levels in mice with diabetes
Anastasia Kuznetsova, N+1
Swiss scientists have delivered cells containing a photosensitive structure capable of activating the production of glucagon-like peptide-1 under the skin on the back of mice. Under the influence of light from the diodes of smart watches attached to the animals' backs, the cells began to produce this hormone. 12 days after such exposure, the mice had a decrease in blood glucose. The study was published in Nature Communications (Mansouri et al., Smart-watch-programmed green-light-operated percutaneous control of therapeutic transgenes).
Drawings from an article in Nature Communications.
In recent years, there have been more and more works in the field of optogenetics. Scientists have learned how to deliver light-sensitive ion channels to cells, which can be activated by radiation of a certain wavelength. Recently, we wrote how, with the help of optogenetics, scientists managed to restore vision to a blind man. The researchers delivered viral vectors encoding a red-light-sensitive ion channel to retinal ganglion cells. In another study, infrared light was used to stimulate the motor areas of the brain of mice to which opsins were delivered. Most often, channels sensitive to ultraviolet, blue, and red are used in research, and green light is used less often.
Some smartwatches, such as the Apple Watch, are equipped with diodes that emit green light, which registers changes that occur when small blood vessels are filled with blood. Scientists came up with the idea that the green light from the clock can be used to control the function of cells implanted under the skin. They used the cobalamin-binding domain of the protein CarH of the bacterium Thermus thermophilus. In the dark, it gathers into a dimer of dimers when it attaches to deoxyadenosincobalamin (the active form of vitamin B12). When green light hits this tetrameric structure, it breaks up into monomers.
Swiss scientists led by Martin Fusseneger have created a molecular structure from the cobalamin-binding domain of the CarH protein and a transactivator. When the tetrameter dissociates into monomers under the influence of green radiation, the transactivator is transferred to the cell nucleus and activates gene expression. Cells begin to produce glucagon-like peptide-1.
The mechanism of the molecular structure.
These cells were then injected into mice with diabetes under the skin of the back. The animals were put on smart watches in such a way that the light from them fell on the site of the introduction of cells. The researchers activated a standard running training program in the watch.
After 12 days, animals implanted with modified cells had high levels of glucagon-like peptide-1 (p < 0.01), as well as low blood glucose levels (p < 0.0001) compared to the control group.
The researchers pay attention to the fact that their molecular design does not need special devices to work, the green set emitted by the smartwatch is enough. Integration of such a system with blood glucose sensors could help diabetic patients maintain glucose levels at normal levels. Now scientists are faced with the task of ensuring the long-term existence of cells under the skin and reducing their immunogenicity.
Glucagon-like peptide-1 and its agonists are often used to treat diabetes and obesity. Recently, the FDA approved a drug for the treatment of obesity based on semaglutide, an agonist of the glucagon–like peptide-1 receptors. It has shown its effectiveness in clinical trials: in people who took it, body weight decreased by 12.4 percent over the year compared to people who received a placebo.
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