Cardiomyocyte-specific deletion of STING improves cardiac function, glucose homeostasis, and wound healing in diabetic mice

Life Sci. 2025 Apr 1:366-367:123470. doi: 10.1016/j.lfs.2025.123470. Epub 2025 Feb 15.

Abstract

Aims: The present study aimed to investigate the effects and underling mechanisms of cardiomyocyte-specific STING knockout on cardiac function and wound healing in diabetes.

Materials and methods: In this study, type 2 diabetes was induced in cardiomyocyte-specific STING knockout mice using a combination of a high-fat diet and streptozotocin. Cardiac function and remodeling were assessed by echocardiography and histopathological analysis. Glucose homeostasis was evaluated through insulin sensitivity tests and intraperitoneal glucose tolerance tests. Wound healing was quantified by measuring the wound area in diabetic mice.

Key findings: The results demonstrated that STING deletion in cardiomyocytes improved cardiac function in diabetic mice, which was accompanied by enhanced insulin sensitivity and improved glucose tolerance. Furthermore, the deletion of STING partially mitigated mitochondrial dysfunction in the myocardium. STING knockout in cardiomyocytes also facilitated angiogenesis and wound healing in diabetic mice.

Significance: Our findings suggest that cardiomyocyte-specific STING deletion enhances cardiac function, glucose homeostasis, and wound healing, indicating that targeting STING in the heart may serve as a promising therapeutic strategy for managing diabetes mellitus.

Keywords: Diabetes; Diabetic cardiomyopathy; Glucose homeostasis; Wound healing.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental* / genetics
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Experimental* / physiopathology
  • Diabetes Mellitus, Type 2* / metabolism
  • Diabetes Mellitus, Type 2* / physiopathology
  • Diet, High-Fat
  • Glucose* / metabolism
  • Homeostasis
  • Insulin Resistance
  • Male
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocytes, Cardiac* / metabolism
  • Myocytes, Cardiac* / pathology
  • STING Protein
  • Wound Healing* / physiology

Substances

  • Membrane Proteins
  • Glucose
  • Blood Glucose
  • Sting1 protein, mouse
  • STING Protein