The discovery of a new gene called ACSL5 could lead to new treatments for insulin resistance and type 2 diabetes, research suggests.
Scientists at The Children’s Hospital of Philadelphia report that the ACSL5 gene codes for a protein that regulates how the body responds to insulin.
They used a gene editing tool called CRISPR in this study, which uses three-dimensional structural biology to determine what happens at a molecular level. CRISPR has been used in previous research to modify human T cells to protect against diseases such as type 1 diabetes.
Lead study author Struan F.A. Grant, PhD, and colleagues wanted to investigate if the biological functions involved in type 2 diabetes could be used to develop more effective therapies.
Using a technique called circularized chromosome conformation capture, or 4C, Grant’s team used colon-derived cells to edit a variant within the gene TCF7L2. In 2006, Grant discovered that this variant in TCF7L2 raised the risk of type 2 diabetes.
After deleting the variant, the researchers used 4C to examine which interactions involved direct physical contact between sections of DNA.
They found that ACSL5 was strongly regulated by the TCF7L2 gene, and plays a role in lipid metabolism. The findings led them to hypothesise that developing drugs to target ACSL5 could increase insulin sensitivity, which is an underlying issue in type 2 diabetes.
“As we continue to better understand the biological mechanisms functioning in type 2 diabetes, we expect to find better strategies for treatment,” said Grant.
“This well-known genomic location harbours an especially strong signal, and may control multiple other genes, yet to be identified.
“In addition, we still don’t know which specific tissue or tissues that these T2D-related signals operate in to affect patients – whether they act primarily in the gut, in the liver, in adipose tissue or on beta cells in the pancreas.”
The studywas published in the journal Diabetologia.

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