Elevated PEDF promotes the occurrence of diabetes mellitus via suppressing GSIS by downregulating the SNARE complex

Type 2 diabetes mellitus (T2DM) is a major global public health burden. The mechanisms through which glucose-stimulated insulin secretion (GSIS) can be suppressed in individuals with obesity-derived type 2 diabetes mellitus (T2DM) have not been elucidated. Compared to normal subjects, the expression of pigment epithelium-derived factor (PEDF) is upregulated in the islets of patients with obesity and T2DM. However, the role of PEDF in β-cells is unclear. This study employed male PEDF transgenic and knockout mice to assess β-cell function through oral glucose tolerance tests and GSIS assays. Complementary cell line experiments elucidated underlying mechanisms, collectively demonstrating the role of PEDF in regulating insulin secretion. PEDF suppressed GSIS by downregulating the SNARE complex, which suppresses the PI3K/Akt signaling pathway. Thus, targeting PEDF is a potential therapeutic strategy for treating T2DM.