Pancreatic stellate cells reduce insulin expression and induce apoptosis in pancreatic β-cells

Islet fibrosis, pancreatic β-cell dysfunction, and β-cell apoptosis are features of pancreatic diabetes and type 2 diabetes; however, the underlying mechanisms remain largely unknown. We hypothesized that pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, might affect the phenotype of pancreatic β-cells. α-Smooth muscle actin (a marker of activated PSC)-positive cells were found within and around the fibrotic islets. Indirect co-culture with PSCs reduced insulin expression and induced apoptosis in RIN-5F pancreatic β-cells. Induction of β-cell apoptosis was associated with activation of the caspase pathway and mitochondrial depolarization. Diphenylene iodonium, an inhibitor of PSC activation, inhibited islet fibrosis and protected islets in vivo. Our findings suggest a novel mechanism linking PSCs, islet fibrosis, and diabetes mellitus.