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. This study examined how the β-adrenergic receptor agonist isoprenaline (ISO) protected against DKD by regulating the 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 signalling 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.