2730-LB: Macrophage GIPR Promotes Diabetic Wound Healing via AMPK–Mitochondrial Axis

Introduction and Objective: GIPR is a novel metabolic drug target, yet its role in dermal macrophages (DMs) during diabetic wound healing is unknown. We studied whether DM GIPR regulates diabetic wound via metabolic reprogramming. Methods: Myeloid GIPR KO and controls received STZ, then excisional wounds. Closure, CD31/collagen, M1/M2 markers and ROS were measured. DMs underwent RNA-seq, Seahorse, JC-1 and WB to assess metabolic profiles. Local AMPK agonist EX229 was delivered for therapy. Results: GIPR KO delayed diabetic wound closure, reduced angiogenesis and collagen, and increased inflammation. KO DMs were M1-biased with higher ROS. RNAseq, seahorse and JC-1 showed suppression of AMPK and OXPHOS. WB showed reduced p-AMPK. Local EX229 restored M2 features and rescued healing. Conclusion: DM GIPR sustains AMPK-mitochondrial homeostasis in diabetic repair. AMPK activation is a new potential therapy. Disclosure Y. Tu: None. C. Zheng: None.