Study uncovers pancreas cell type-specific activities of IL18

Both type 1 and type 2 diabetes are characterized by the loss of β cells and insulin secretion. Regenerating β cells from other cell types, such as α cells, has been proposed as a potential therapeutic strategy for diabetes. Inflammation is thought to be connected to diabetes progression, but many questions remain about the role of specific markers of inflammation, such as interleukin 18 (IL18) in the disease and in specific cell types. In a new study, researchers have found that in human and mouse pancreases, α cells express IL18, acinar cells express traditional IL18 receptors, and β cells express an alternative IL18 receptor known as the Na-Cl co-transporter (NCC). The team’s findings suggest that IL18, together with the glucagon-like peptide-1 (GLP1) from α cells, uses NCC and GLP1 receptor on β cells for β-cell development, insulin secretion, and insulin signaling. Like GLP1 agonists, IL18 may have therapeutic potential for patients with obesity and diabetes. Yet, interruption of IL18 interactions with its receptors has been shown to be effective at reducing atherosclerosis in experimental models. Therefore, targeting IL18 in patients with cardiovascular disease may damage β-cell functions.

“These findings provide insights into the role of IL18 signaling in regulating islet β cell proliferation and may help guide future efforts to protect these IL18 pathways as a potential strategy to expand β cells and increase islet mass in diabetes,” said senior author Guo-Ping Shi, ScD, a principal investigator in the Brigham’s Division of Cardiovascular Medicine.

Read more in Developmental Cell.