Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns
Authors' conclusion
In conclusion, our study shows that CANA ameliorates DKD by inducing fasting-like and aestivation-like metabolic patterns. Furthermore, DKD was ameliorated by glycine supplementation, and the beneficial effects of glycine were probably due to the activation of the AMPK/mTOR pathway.
Study context
- Population
- Participants with T2D and kidney disease (11 women); db/db mice; human proximal tubular epithelial (HK-2) cells11 women
- Participants
- 35 participants
- Comparison
- Canagliflozin (CANA) 100 mg/day, baseline vs 12-week follow-up
- CANAn = 35
- Outcome
- Metabolic effects of CANA in diabetic kidney disease (DKD)
- Follow-up
- 12 weeks
Methodological detailsuntargeted and targeted metabolomics, db/db mice, HK-2 cells
- Untargeted and targeted metabolomics
- Db/db mice
- HK-2 cells
Main finding
As reported in the abstract
- Untargeted metabolomics: downregulated glycolysis and upregulated fatty acid oxidation
- Targeted metabolomics: significant upregulation of glycine
- CANA regulated metabolic reprogramming in db/db mouse kidneys; glycine, serine and threonine metabolism pathways and glycine metabolite significantly upregulated
- Glycine supplementation ameliorated renal lesions in db/db mice by inhibiting food intake, improving insulin sensitivity and reducing blood glucose
- Glycine supplementation improved apoptosis of HK-2 cells via the AMPK/mammalian target of rapamycin (mTOR) pathway
Further findings
HbA1c, baseline to 12 weeks
- HbA1c significantly reduced, median (IQR) from 49.0 (44.0-57.0) mmol/mol (7.9%, [7.10-9.20%]) to 42.2 (39.7-47.7) mmol/mol (6.8%, [6.40-7.70%])
Urinary albumin/creatinine ratio, baseline to 12 weeks
- Reduced from 67.8 (45.9-159.0) mg/mmol to 47.0 (26.0-93.6) mg/mmol
Original publication
Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns. Diabetologia. Published 18 January 2024. doi:10.
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