Hyaluronan induces ERK activation with minimal transcriptomic changes in pancreatic α-cells

Hyaluronan (HA), an extracellular matrix glycosaminoglycan, accumulates in pancreatic islets in patients with T1D and animal models, and has been implicated in promoting chronic inflammation. Inhibition of HA synthesis in T1D model mice attenuates disease progression, suggesting that HA accumulation contributes to disease deterioration.

While b cells are selectively targeted and depleted in T1D, a cells that secrete glucagon are relatively preserved from immune-mediated destruction. Therefore, we hypothesized that accumulated HA may impair a-cell function and thereby contribute to T1D pathophysiology. To investigate this, we performed RNA sequencing on HA-treated a-cell lines and compared the transcriptional profiles to publicly available datasets from a cells isolated from T1D donors.