Gene discovered using DNA analysis may help prevent steroid-induced diabetes

By Elissa Wolfson, The Science Advisory Board assistant editor

June 14, 2023 -- Scientists from Australia's Garvan Institute of Medical Research and Adelaide Medical School found that a gene called RELA, known to regulate inflammation, also plays an essential role in maintaining normal blood sugar levels. The study, funded by the National Health and Medical Research Council and the Australian Juvenile Diabetes Research Foundation and published Wednesday in Diabetologia, may contribute to preventing side effects from corticosteroid treatment for inflammation.

Steroid-induced diabetes, a temporary form of diabetes, affects up to half of hospital patients treated with high-dose steroids. This class of drugs, called corticosteroids, is commonly used to reduce inflammation in patients with conditions including arthritis or asthma. Although central to the body's defense mechanisms, inflammation can cause harm and autoimmune disease when unchecked, making it a key target for therapy.

Steroids help prevent inflammation by targeting the RELA gene, which regulates the expression of proteins involved in inflammation. However, within weeks of starting or increasing corticosteroid medications, patients can develop steroid-induced diabetes. Previously, the link between inflammation and diabetes was not well understood.

The researchers sought to learn about the mechanisms behind inflammation and how to better target it. Using mice to study the genes that control inflammation, they found that removing the RELA gene led to abnormally high blood sugar levels. Mice lacking the RELA gene became prediabetic due to impaired insulin secretion in the pancreas.

The researchers next investigated the cells lacking RELA using next-generation DNA analysis. They found that the protein that RELA produces switches on a genetic program required for beta cells in the pancreas to produce insulin. This indicated that, although inflammation and diabetes are linked, RELA regulates blood sugar and inflammation independently. The findings suggest that RELA plays an essential role in keeping blood sugar levels normal, even when there is no inflammation.

The discovery sheds new light on the complex network of factors governing glucose metabolism, and how it goes awry in diabetes. The knowledge that RELA coordinates the expression of other genes essential for glucose control may have implications for understanding and preventing steroid-induced diabetes.

The researchers said that, while their research has uncovered a fundamental facet of how the body maintains normal blood glucose levels, their results could also help improve the clinical management of patients who require long-term or high-dosage corticosteroid treatment. They hope their work furthers the development of more tailored therapies for these patients, which could potentially be achieved using treatment strategies that prevent inflammation without targeting RELA.

"By understanding how insulin-producing cells and systems in the pancreas are regulated by RELA, it may be possible to balance the inhibition of inflammation without disrupting the function of insulin-producing cells," senior author Shane Grey, head of Garvan's Transplant Immunology Lab, noted in a statement. "This could lead to the development of medications that reduce inflammation without bringing on steroid-induced diabetes as a side effect."

Gene variant map helps diagnose hereditary diabetes
University of Copenhagen researchers are using high-throughput experiments to explore connections between inherited diseases and a specific gene called...
Tiny but mighty gene fragments maintain blood glucose levels
Researchers have discovered that tiny gene fragments called microexons are prevalent in pancreatic islets – tissues that host beta cells which produce...
Gene in beta cells enables release of insulin, offers potential diabetes therapy
An international team of scientists has shown that the gene Wnt Family Member 4 in beta cells enables them to sense glucose and release the hormone insulin,...
CHOP spots genetic variants, gene pairings involved in type 2 diabetes
Children's Hospital of Philadelphia (CHOP) researchers used 3D mapping at a microscopic level to identify genetic variants and corresponding target gene...
Beta cell gene deletion stops type 1 diabetes in mice, suggesting new way to prevent disease
Deleting a proinflammatory gene in the beta cells of pre-diabetic mice stops the development of type 1 diabetes, pointing to a potential way to prevent...
Researchers grow functional pancreatic beta cells from stem cells
A research group has demonstrated that stem cells can form cells that closely mimic normal pancreatic islets, in terms of both structure and function....
Human Cell Design launches advanced human beta cell model
Human Cell Design has launched Endoc-BH5, the fifth version of its model of ready-to-use functional human pancreatic beta cells.
NIH branch institute launches consortium for pancreatic research
As part of the Impact of Genomic Variation on Function Consortium, researchers at the University of California, San Diego School of Medicine will receive...

Copyright © 2023

Science Advisory Board on LinkedIn
Science Advisory Board on Facebook
Science Advisory Board on Twitter