Chronic hyperinsulinemia accelerates adipose senescence via mitochondrial dysfunction and cGAS-STING signalling.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Prediabetes and Type 2 Diabetes represent major global health challenges and have escalated to pandemic levels. Adipose tissue functions as a critical endocrine organ, playing a central role in maintaining glucose homeostasis during fasting, feeding, and stress responses. In this study, we demonstrated that prolonged chronic hyperinsulinemic stress increases the burden of senescent adipocytes, accompanied by activation of the cGAS-STING signalling pathway. Chronic hyperinsulinemia-induced insulin-resistant 3T3-L1 and human mesenchymal stem cell-derived adipocytes exhibited elevated senescence-associated phenotypes, mitochondrial dysfunction and impaired cellular energetics. Notably, we found that mitochondrial DNA leakage triggered the cGAS-STING pathway in insulin-resistant adipocytes and mouse models. Temporal analysis revealed that mitochondrial dysfunction was detectable at earlier stages of chronic insulin exposure, preceding activation of the cGAS-STING pathway and senescence-associated markers, supporting a progressive model of cellular dysfunction. This phenomenon was also observed in adipose depots of individuals with Type 2 diabetes, underscoring the translational relevance of our findings. Targeting cGAS or STING, either pharmacologically or through genetic silencing, significantly reduced inflammatory and senescence-related features in hyperinsulinemia-induced insul

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.