A distinct role of STING in regulating glucose homeostasis through insulin sensitivity and insulin secretion

Author:

Qiao Jingting1ORCID,Zhang Ziyin23ORCID,Ji Shuhui14ORCID,Liu Tengli56,Zhang Xiaona1,Huang Yumeng1ORCID,Feng Wenli1,Wang Kunling1,Wang Jianyu1,Wang Shusen56,Meng Zhuo-Xian237ORCID,Liu Ming14ORCID

Affiliation:

1. Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin 300052, China

2. Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China

3. Zhejiang Provincial Key Laboratory of Pancreatic Disease of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China

4. Tianjin Research Institute of Endocrinology, Tianjin 300052, China

5. Organ Transplant Center, Tianjin First Central Hospital, Tianjin 300192, China

6. National Health Commission Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Tianjin 300384, China

7. Department of Geriatrics, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China

Abstract

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.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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