Open AccessA distinct role of STING in regulating glucose homeostasis through insulin sensitivity and insulin secretion
Author(s) -
Jingting Qiao,
Ziyin Zhang,
Shuhui Ji,
Tengli Liu,
Xiaona Zhang,
Yumeng Huang,
Wenli Feng,
Kunling Wang,
Yunlong Wang,
Shusen Wang,
Zhuo-Xian Meng,
Ming Liu
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2101848119
Subject(s) - glucose homeostasis , glut2 , biology , homeostasis , medicine , pax6 , endocrinology , transcription factor , insulin resistance , insulin , sting , knockout mouse , glucose transporter , gene , biochemistry , aerospace engineering , engineering
Significance The role of STING in maintaining glucose homeostasis remains unknown. Herein, using global and β-cell–specific STING knockout mouse models, we revealed a distinct role of STING in the regulation of glucose homeostasis through β-cells and peripheral tissues. Specially, while global STING knockout beneficially alleviated insulin resistance and glucose intolerance induced by high-fat diet, it surprisingly impaired islet glucose-stimulated insulin secretion (GSIS). Further analyses revealed that STING deficiency down-regulated expression of β-cell key transcription factor Pax6, impairing Pax6 nuclear localization and binding activity to the promoters of its target genes, including Glut2 and Abcc8, causing impaired GSIS. These data highlight pathophysiological significance of fine-tuned STING signaling in β-cells and insulin target tissues for maintaining glucose homeostasis.