1743-P: STING Mediates Glucose-Induced Insulin Secretion through Pax6

Introduction & Objective: Previous studies have shown that stimulator of interferon genes (STING) plays an important role in regulating glucose homeostasis, including insulin secretion. This study aimed to investigate the role of STING in glucose-induced insulin secretion.

Methods: Rat pancreatic β-cell line INS-1 cells and islets from adult wide-type (WT) mice were cultured with high-glucose (33.3 mmol/L) and low-glucose (2.8 mmol/L) and the expression of STING was detected by RT-PCR and western blotting. Glucose-stimulated insulin secretion (GSIS) tests were measured in islets from global STING knockout (KO) mice or high-glucose-induced islets of WT mice. The involvement of STING and Pax6 was evaluated by infecting islets with STING-overexpression adeno-associated virus (AAV-STING) or AAV-Pax6 in vitro.

Results: STING was highly expressed in pancreatic islets and INS-1 cells, but its levels were reduced in high-glucose-induced islets and INS-1 cells compared to controls. Overexpression of STING could restore GSIS in high-glucose-induced islets of WT mice. In addition, the expression levels of several genes involved in insulin secretion, including Pax6, Abcc8, Kir6.2, were significantly reduced in high-glucose induced islets of WT mice and were increased when STING expression was restored. Moreover, GSIS was significantly decreased in islets from STING KO mice, and the overexpression of either STING or Pax6 resulted in an increased expression of Pax6, Abcc8, Kir6.2 and improved GSIS.

Conclusion: This study provides the first in vitro experimental evidence supporting that STING may play an important role in glucose-induced insulin secretion through transcription factor Pax6.