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Patients on long-term steroid treatment may have metabolic side effects. Researchers from the Helmholtz Zentrum München and the Ludwig Maximilians University of Munich (LMU), partners of the German Diabetes Research Center (DZD), have identified a mechanism that leads to so-called steroid diabetes. Their conclusions have been published in Nature Communications.
"Glucocorticoids such as cortisone have been used for many decades to treat inflammatory diseases such as asthma or rheumatism, and they are the most commonly prescribed anti-inflammatory drugs," says Professor Henriette Uhlenhaut, head of group at the Institute of Diabetes and Obesity IDO) at the Helmholtz Zentrum München and at the gene center of the LMU. "They are also frequently used in autoimmune diseases, organ transplants and cancer.It is estimated that between 1 and 3% of the Western population currently takes these medications, which corresponds to more than One million Germans. "
However, although glucocorticoids are prescribed in a wide range of diseases, their use is limited by the various adverse effects that may occur during treatment, including adverse metabolic effects. Once glucocorticoids bind to their receptor inside the cell, the receptor begins to activate and deactivate many genes. "These include various metabolic genes, which can therefore be at the origin of what is called steroid diabetes," explains Henriette Uhlenhaut.
In the current study, his team – along with colleagues from the Max Delbrück Center for Molecular Medicine in Berlin, the Salk Institute of San Diego and the University of Friborg – sought to identify the exact sequence of events that occurred. occur once steroids have their receptor bind.
"What struck us most is the transcription factor E47, which, along with the glucocorticoid receptor, is responsible for changes in gene expression, particularly in liver cells," explains Charlotte Hemmer, PhD candidate at IDO and first author of the current study. "We were able to identify the underlying pathway by performing genome-wide genetic badyzes and studies."
To corroborate their conclusions, the scientists then examined a preclinical model lacking the E47 gene. "The loss of E47 has effectively protected the negative impact of glucocorticoids, while an intact E47 gene has resulted in metabolic changes such as elevated blood sugar, elevated blood fat levels, or increased blood glucose levels. hepatic steatosis in response to treatment with steroids, "adds Charlotte Hemmer.
The components of the newly discovered mechanism are also kept in humans, Henriette Uhlenhaut and his team, as well as their clinical cooperation partners, now want to know if their results can be translated into human studies. "If this is the case, this could open up new opportunities for therapeutic intervention and the use of safer immunosuppressants in order to combat the side effects of steroid treatment."
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