Isoprenaline alleviates diabetic kidney disease via multi-target inhibition of the cGAS-STING pathway.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and is closely linked to chronic inflammation. The present study examined how the β-adrenergic receptor agonist isoprenaline (ISO) protected against DKD by regulating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway through multiple targets. In a streptozotocin-induced diabetic mouse model, ISO treatment improved glomerulosclerosis, reduced podocyte injury and proteinuria, and suppressed renal inflammation. Network pharmacology and molecular docking suggested that, besides activating ADRB1/2, ISO may interact with AKT1, SRC, GSK3β, and EGFR, which are involved in cGAS-STING signaling regulation. These findings indicate that ISO alleviates DKD by inhibiting excessive activation of the cGAS-STING pathway through multi-target coordination, providing a new perspective for therapeutic development.