Gene Identified as Key Driver of Type 2 Diabetes, Offering Potential for New Therapies

Researchers have identified the SMOC1 gene as a critical factor in the development of type 2 diabetes (T2D), potentially paving the way for therapies that directly address the root cause of beta cell failure.

The study, published today in Nature Communications, found that in individuals with T2D, the SMOC1 gene—typically active only in alpha cells—becomes active in beta cells, which are responsible for producing insulin. This reprogramming transforms beta cells into dysfunctional, alpha-like cells, impairing insulin production and release. Type 2 diabetes affects over 37 million Americans, and current treatments primarily manage symptoms rather than halting disease progression.

Scientists at City of Hope utilized single-cell RNA sequencing to analyze pancreatic tissue from 26 donors, 13 with T2D and 13 without, revealing the gene’s role. “Normally, SMOC1 is active in healthy people’s alpha cells,” explained Dr. Geming Lu, a researcher at City of Hope. “But we saw it start showing up in the diabetic beta cells, too. It should not have been there.” Further laboratory tests confirmed that increasing SMOC1 levels in human beta cells directly led to decreased insulin production and cellular transformation. You can learn more about the role of beta cells at the National Institute of Diabetes and Digestive and Kidney Diseases.

Researchers also discovered significantly higher levels of the SMOC1 protein within the beta cells of diabetic patients. Senior research associate Randy Kang stated, “The SMOC1 gene has barely been studied in diabetes. Based on these properties, we suspect SMOC1 strongly influences the differentiation and function of beta cells.” This discovery suggests that blocking SMOC1’s action could protect insulin-producing cells and potentially halt or reverse the progression of T2D, offering a new therapeutic avenue beyond existing treatments like GLP-1 receptor agonists.

The research team is now focused on developing a drug to inhibit SMOC1 and is in the early stages of therapeutic development, with no approved gene therapies currently targeting the gene for T2D.