Potential Role of Aerobic Exercise in Attenuating Diabetic Cardiomyopathy via Modulation of P2X4-Mediated NLRP3 Inflammasome Activation and Pyroptosis.

ABSTRACT: Diabetic cardiomyopathy (DCM) is a common diabetic complication associated with chronic low-grade inflammation. Exercise is an effective therapy for DCM, though its mechanisms remain unclear. Here, we demonstrate that exercise mitigates pyroptosis in DCM, potentially by modulating P2X4. Exercise prevented the upregulation of P2X4 and PANX1, inhibited NLRP3 activation, and reduced GSDMD and IL-1β cleavage in DCM mouse hearts, without altering P2X7 levels. In vitro, high glucose alone did not induce significant H9C2 cell death or increase P2X4/P2X7 expression. However, palmitic acid promoted a concentration-dependent increase in P2X4 and NLRP3 expression, caspase-1 activity, and cell necrosis, indicating that lipids drive pyroptosis. A high-fat diet (HFD) model further confirmed a positive c

SUBMITTER: Liu Z 

PROVIDER: S-EPMC12659644 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature