– In people with type 2 diabetes, the VPS39 gene is significantly less active in muscle cells than it is in healthy people, and stem cells with less VPS39 do not form new muscle cells as much. At the same time, VPS39 is of great importance to the ability of muscle cells to absorb sugar and build new muscle, says Charlotte Ling, professor of epigenetics at the Diabetes Center at Lund University, who led the new international study published in Nature Communications.
Our study is the first ever to link the VPS39 gene with type 2 diabetes.
Disturbed muscle function
In type 2 diabetes, the ability to produce insulin is impaired, and the disease involves chronic high blood sugar. The ability of tissues to use the available insulin is also affected. Muscles are worse at absorbing sugar from food, while muscle function and muscle strength are impaired.
Muscle consists of a mixture of types of fibers with different properties. Throughout life, muscle tissue has the ability to form new muscle fibers. With regard to muscle fibers, there are immature muscle stem cells that are activated in connection with, for example, injury and physical exercise. In the current study, the researchers wanted to investigate whether epigenetic patterns in muscle stem cells could provide answers as to why muscle dysfunction occurs in type 2 diabetes and what mechanisms are behind it.
Alter the genome without changing the code
Epigenetics is the link between the environment and inheritance that controls the function of our genes and thus our cells.
Epigenetics means “over genes” and relates to genome modifications that do not alter the genetic code. In epigenetics, researchers study our genes (genetics) and beyond, that is, the mechanisms that control genes and which can be influenced by the environment and lifestyle. Epigenetic modifications are about how DNA is read and when it is expressed, that is, which genes are turned on or off and when they are turned on.
Source: Charlotte Ling and Joanna Sall Cernevi
Two groups were included in the study: 14 study participants with type 2 diabetes and 14 healthy people in the control group. Participants in the groups were matched, among other things, by age, gender, and body mass index (BMI).BMI). The researchers studied the epigenetic changes in muscle stem cells from both groups, and under exactly the same conditions, they cultured mature muscle cells and compared them.
In total, the researchers identified 20 genes whose gene expression varied between groups in both immature muscle stem cells and mature muscle cells. The researchers also compared the epigenetic patterns of pre- and post-cell muscle cellsDevelopment (differentiation) To mature muscle cells.
It does not regulate naturally
– Despite the fact that the muscle stem cells of both groups grew under completely identical conditions, we saw more than twice as many epigenetic changes in type 2 diabetes during differentiation from muscle stem cells to the mature muscle cell. Charlotte Ling says genes for muscles were not regulated normally and epigenetics did not function normally in the cells of type 2 diabetes patients.
The study clearly showed that muscle stem cells that lack the function of the VPS39 gene, which is lower in type 2 diabetes, also lack the ability to form new mature muscle cells. This is because muscle stem cells that lack VPS39 due to altered epigenetic mechanisms cannot alter their metabolism in the same way that muscle stem cells change from healthy individuals – so the cells remain immature or disintegrate and die, says Joanna Sal Sernevi, a postdoctoral fellow at Lund. University.
Sitting still increases your risk of developing type 2 diabetes
The risk of developing type 2 diabetes is partly genetic and influenced by genetics, environment, and lifestyle. One in eleven adults in the world suffers from the disease, and with an increasingly older population and a sedentary lifestyle, the incidence increases. Epigenetics involves genetic but reversible changes in gene expression that are independent of changes in the DNA sequence. Genetic modifications act as a link between genes (heredity) and the environment. The epigenetic mechanisms and modifications are influenced by factors such as exercise, diet, age, chemicals and drugs, and regulate when and how much different genes should be activated.
Source: Charlotte Ling and Joanna Sall Cernevi
To confirm the results, the researchers also used animal models with mice containing a reduced amount of the VPS39 gene to mirror disease. Mice also altered gene expression and impaired sugar uptake in muscle tissue, just like those with type 2 diabetes.
New treatment options
The comprehensive study is a collaboration between Swedish, Danish and German researchers. The researchers themselves believe the results open new possibilities for treating type 2 diabetes.
The genome, our DNA, cannot be changed, despite the science of epigenetics. With this new knowledge, it is possible to alter the dysfunctional epigenetic inheritance that occurs in type 2 diabetes. By, for example, regulating proteins or stimulating or increasing the amount of the VPS39 gene, it will be possible to influence the ability of muscles to regenerate and absorb sugar, as Charlotte Ling says.
The impairment of VPS39 observed in type 2 diabetes impairs muscle stem cell differentiation by altered autophagy and epigenetics.And the (Cagsa Devgard, Joanna Sal Sernevi, Anna Benrik, Christa Broholme, Peter Volkov, Alexander Perveliev, Tora Ida Henriksen, Yanling Wu, Line Hegurt, Charlotte Bruns, I. Hanson, Maria Pedersen, Jens U Worthner, Klaus Pfeiffer, Emma Nelson, Alan Fage, Elizabeth Steiner, Victorin, Carolina Birx, Camilla Shell, Charlotte Ling), Nature Communications.
Charlotte LingCharlotte Ling, Professor of Epigenetics at Lund University Diabetes Center (LUDC), [email protected]
Joanna Sal Cernevi, Postdoctoral Fellow at Lund University Diabetes Center (LUDC), [email protected]