Purpose: Investigate the mechanism of how sodium butyrate (NaBut) improves mitochondrial function and kidney tissue injury in diabetic kidney disease (DKD) via the AMPK/PGC-1α pathway.
Methods: Assess the effects of NaBut on glucose and insulin tolerance, urine, and gut microbial composition in db/db and db/m mice. Use flow cytometry and western blotting to detect the effects of NaBut on apoptosis, kidney mitochondrial function, and AMPK/PGC-1α signaling. Use HK-2 cells induced by high glucose (HG) to establish the DKD model in vitro and detect changes in the AMPK/PGC-1α signaling pathway and mitochondrial function after NaBut intervention.
Results: NaBut attenuated blood glucose levels and reversed increases in urine and serum levels of glucose, BUN, Ucr, TG, TC, and UAE in db/db mice. NaBut improved insulin tolerance, reversed PGC-1α and p-AMPK expression level in the kidneys of db/db mice, and improved lipid accumulation and mitochondrial function. NaBut was able to reverse the effects of elevated glucose, compound C, and siRNA-PGC on ROS and ATP levels. Additionally, it increased protein expression of PGC-1α and p-AMPK.
Conclusion: NaBut activates the kidney mitochondrial AMPK/PGC-1α signaling pathway and improves mitochondrial dysfunction in DKD, thus protecting kidney tissue in vitro and in vivo.
Keywords: AMPK/PGC-1α pathway; Sodium butyrate; diabetic kidney disease; mitochondrial function.