Electroacupuncture protects gastric Cajal cells by reducing macrophage pyroptosis in diabetic gastroparesis

Figure 1 Proposed mechanistic hypothesis in diabetic gastroparesis. In the diabetic gastroparesis setting, M2 macrophages usually recognize and phagocytose apoptotic interstitial cells of Cajal (ICCs). However, upregulation of Gasdermin D triggers pyroptosis, impairing mitochondrial function and reducing phagocytic efficiency. The resulting accumulation of damaged DNA from incompletely cleared ICCs activates the cyclic GMP-AMP synthase-stimulator of interferon genes inflammatory pathway, leading to the release of proinflammatory mediators and further apoptosis of ICCs. The dashed section represents assumptions based on the literature. ICC: Interstitial cells of Cajal; IL: Interleukin; GSDMD-N: Gasdermin D-N terminal domain; NLRP3: NOD-like receptor family pyrin domain containing 3; mtDNA: Mitochondrial DNA; cGAS: Cyclic GMP-AMP synthase; STING: Stimulator of interferon genes; IRF3: Interferon regulatory factor 3; NF-κB: Nuclear factor-κB; TBK1: TANK-binding kinase 1; GSDMD: Gasdermin D.