Abstract: FR-PO0185
Semaglutide with Exercise Training: Synergistic Combination Against Mitochondrial Cellular Injury in Diabetic Kidney Disease Morbidity
Session Information
- Diabetic Kidney Disease: Metabolic, Mitochondrial, and Inflammatory Mechanisms
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 601 Cardiovascular-Kidney-Metabolic Health: Basic
Authors
- Silva, Eloiza De Oliveira, Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo, São Paulo, SP, Brazil
- García, Jessica Paola, Universidade de Sao Paulo, São Paulo, SP, Brazil
- Santos, Luciana Soares Costa, Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo, São Paulo, SP, Brazil
- Vattimo, Maria De Fatima, Universidade de Sao Paulo, São Paulo, SP, Brazil
Background
Diabetic kidney disease (DKD) remains a leading complication of type 2 diabetes mellitus (T2DM). We tested whether semaglutide (GLP-1 RA) combined with moderate physical training (PT) provides additive renoprotection in experimental T2DM and whether semaglutide directly protects HK-2 tubular cells exposed to high glucose.
Methods
The rats were allocated into six groups: control, diabetic, and treated diabetic. The interventions lasted 28 days Rybelsus. Renal function, hemodynamics, and oxidative profile were evaluated. HK-2 cells were cultured in normal or high glucose and treated with semaglutide; MTT, LDH, and TGF-β levels were measured.
Results
T2DM reduced inulin clearance compared to controls (0.26 ± 0.09 mg/min vs. 0.94 ± 0.16 mL/min). Combination therapy improved this parameter by 0.62 ± 0.12 mL/min. In addition, it reduced renal vascular resistance from 78.05 ± 16.8 to 20.5 ± 2.2 mmHg/mL/min, respectively, and improved renal blood flow by 1.77 ± 0.32 and 5.45 ± 0.10 mL/min, respectively (p < 0.05). Combination therapy reduced the oxidative profile and restored thiol levels. T2DM increased IL-1β and TGF-β, while combination therapy reduced IL-1β and TGF-β. In HK-2 cells, high glucose concentration increased MTT signaling, LDH release, and TGF-β Semaglutide reduced these changes.
Conclusion
Semaglutide, combined with moderate PT, conferred renal protection that could not be interpreted solely as a consequence of weight loss or glycemic control, attenuating significant renal alterations associated with diabetic nephropathy. Importantly, semaglutide also protected HK-2 tubular cells by neutralizing the metabolic hyperactivation induced by high glucose concentration. These findings demonstrate semaglutide combined with PT as renoprotective strategy against both glomerular and tubular injury in DKD.
Funding
- Private Foundation Support