Researchers determine the mechanism responsible for “steroid diabetes”


As its name implies, steroid diabetes is a form of diabetes that stemmed from the use of certain steroid drugs. A German study recently found how steroid-based drug treatment could eventually lead to the appearance of the metabolic disorder.

Researchers at the Institute for Diabetes and Obesity (IDO) examined a type of steroid called glucocorticoids. These steroids are often used as part of pharmaceutical drugs for managing symptoms caused by the excessive or unnecessary inflammation of cells and tissues.

“Glucocorticoids such as cortisone have been used to treat inflammatory diseases such as asthma or rheumatism for many decades, and they are the most commonly prescribed anti-inflammatory drugs,” explained IDO researcher Henriette Uhlenhaut. “They are also frequently used in autoimmune diseases, organ transplantations and cancer.”

Experts believe that anywhere from one to three percent of the population of Western countries are taking glucocorticoids as treatments for various diseases. In Germany alone, there are more than one million people who have been prescribed these steroids. (Related: Did you know that turmeric is just as effective as 14 pharmaceutical drugs?)

Steroid-based treatments can ruin the metabolism of patients

Glucocorticoids are recommended by healthcare providers for all kinds of medical conditions. But they have also been shown to cause numerous side effects, including altering the metabolism of the patient during the treatment period.

These steroids worked by binding to their target receptor within the cell. Once bound, a receptor would activate and deactivate various genes. Many of these genes were involved in metabolic processes.

When metabolic genes went awry, they could disrupt the normal balance of the metabolic system. If taken for too long or in large amounts, glucocorticoids could bring about the onset of diabetes, a serious metabolic disorder.

With this concern in mind, the IDO researchers launched a study to identify the specific sequence of events that took place during the moment that the steroids bound themselves to their receptor. They worked alongside their counterparts from the Max Delbrück Center for Molecular Medicine, the Salk Institute for Biological Studies, and the University of Freiburg.

By disrupting metabolic genes, glucocorticoids can cause “steroid diabetes”

“What struck us most was the E47 transcription factor, which — along with the glucocorticoid receptor — is responsible for the changes in gene expression, particularly in liver cells,” said IDO researcher Charlotte Hemmer, who served as the first author of the new study. “We were able to identify the underlying pathway by conducting genome-wide analyses and genetic studies.”

A transcription factor is a molecule that controls the activity or “expression” of a gene. In this case, the E47 transcription factor controlled the E47 gene, which is responsible for certain metabolic processes.

The IDO-led research team sought to expand on the initial findings of their experiment. They created a model using mice that did not have the E47 gene and treated the animals with glucocorticoids. Their follow-up testing showed that the lack of the E47 gene kept the metabolism of the mice safe from glucocorticoids.

In comparison, normal mice that retained their E47 gene experienced alterations to their metabolism. Their blood sugar levels and blood fat levels went up, and harmful fatty acids accumulated in their livers. These issues happened to be symptoms of diabetes.

The E47 gene is also found in humans. The researchers are planning to see if their discovery in mice could be applied to people as well.

In the meantime, it might be wise to stop using glucocorticoids as anti-inflammatory medicine. Instead, look for alternative ways to reduce inflammation that do not affect metabolic genes. Diabetes is a very serious disease and a very steep potential price to pay for relief from inflammatory conditions.

Sources include:

ScienceDaily.com

Nature.com



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