Dec 08, 2021

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According to the World Health Organization, about 1.5 million people around the world died from complications of type-2 diabetes in diabetes in 2019. It is estimated that 463 million people are living with diabetes all over the world; many people don’t even know they have it. 


The chronic disease, caused by insulin resistance and reduction of cells’ ability to absorb sugar, is characterized by increased blood sugar levels. Its long-term complications include heart disease, strokes, damage to the retina that can result in blindness, kidney failure and poor blood flow in the limbs that could lead to amputations of the limbs, especially the feet and legs. It is currently treated by a combination of lifestyle changes, medications and insulin injections, but ultimately, if not treated properly, it means that sufferers live a decade less than the average in life expectancy.

Skeletal muscle tissue participates in various functions in the body. It comprises about 40% of total body weight and provides stability and movement to the skeleton. Skeletal muscle also plays a major role in glucose balance, glycogen and lipid metabolism and more. In recent years, the skeletal muscle tissue has been identified as a secretory organ; when it contracts, it releases muscle-specific cytokines and myokines that have local and/or systemic effects/ The skeletal muscle tissue is responsible for about 80% of infused glucose uptake. Skeletal muscle insulin resistance is a key defect in type-2 diabetes and obesity. The clinical guideline for treatment is to normalize glycemia and thus minimize the chronic diabetes–related complications that can lead to medical disability, reduction in life expectancy and high health costs. 


Despite numerous treatment options, patients often fail to reach target blood sugar values. To improve the overall patient health, there is a need for developing long-acting, stimuli-responsive and alternate delivery systems.


A novel approach to treating type-2 diabetes is being developed by a team at the Technion-Israel Institute of Technology in Haifa led by Prof. Shulamit Levenberg and her doctoral. student Rita Beckerman from the stem cell and tissue engineering laboratory in the Technion’s Faculty of Biomedical Engineering. 


The innovative technique involves using an autograft (in which tissue is moved from one part of the body to another) of muscle cells engineered to take in sugar at increased rates. Mice treated in this manner displayed normal blood sugar levels for months after a single procedure. The group’s findings were recently published in Science Advances under the title “GLUT4-overexpressing engineered muscle constructs as a therapeutic platform to normalize glycemia in diabetic mice.” 


Muscle cells are among the main targets of insulin, and they must absorb sugar from the blood. In their study, Levenberg’s group isolated muscle cells from mice and engineered these cells to present more insulin-activated sugar transporters (GLUT4). These cells were then grown to form an engineered muscle tissue and finally transported back into the abdomen of diabetic mice. 


The engineered cells not only proceeded to absorb sugar correctly, improving blood sugar levels, but also induced improved absorption in the mice’s other muscle cells via signals sent between them. After this one treatment, the mice remained cured of diabetes for four months – the entire period they remained under observation. Their blood sugar levels remained lower, and they had reduced levels of fatty liver normally displayed in type-2 diabetes. 

“By taking cells from the patient and treating them, we eliminate the risk of rejection,” Levenberg explained. These cells can easily integrate back into being part of the body and respond to the body’s signaling activity. 

An effective treatment – one that is a one-time treatment rather than daily medication – could significantly improve both quality of life and life expectancy of those who have diabetes. The same method could also be used to treat various enzyme-deficiency disorders, the researchers said.