Study links gene network and pancreatic beta cell defects to type 2 diabetes

Type 2 diabetes affects almost 35 million people in the United States, increasing the risk of death and causing serious health complications including blindness, kidney failure, heart disease and stroke, according to the Centers for Disease Control and Prevention. Studies have linked hundreds of sites in the genome to increased risk of type 2 diabetes, but 90% of the sites are located in non-coding rather than protein-coding regions of DNA. “How this genetic variation at the population level relates to molecular changes in gene expression, tissue architecture and cellular physiology in type 2 diabetes is not well understood,” said Marcela Brissova, Ph.D., research professor of Medicine at Vanderbilt University Medical Center and lead co-corresponding author of a new study. 

Although processes that contribute to type 2 diabetes have been studied in rodent models, human islets—the mini-organs that house beta cells along with a number of other cell types—differ from rodent islets in multiple ways. Therefore, Brissova and her team used the Vanderbilt Pancreas Biorepository to study pancreatic tissue and isolated islets from donors with early-stage type 2 diabetes and non-diabetic controls. Their comprehensive study integrated multiple analytic approaches, including analyzing islet function, gene expression (which genes are turned “on” or “off”), islet architecture, and population genetics.

The study, published in the journal Nature, links a regulatory gene network and functional defects in insulin-producing pancreatic beta cells to type 2 diabetes. In addition, their “data indicate that beta cell loss is not a major component in disease pathogenesis in early-stage type 2 diabetes,” says Diane Saunders, Ph.D., a first author on the paper. The study lays the foundation for identifying additional early disease-driving events for type 2 diabetes, and it also provides a template for identifying regulatory networks that drive other diseases.

Source: Vanderbilt University Medical Center, Medical Xpress, November 8, 2023; see source article