Figure 3.

Potential molecular mechanisms of SGLT1 inhibition in diabetes-related heart injury. SGLT1 inhibition can reduce cardiomyocyte fibrosis and apoptosis through JNK and p38 MAPK pathways, as well as block Rac1 activation and p47phox translocation to reduce NOX2 activation and ROX production, thus reducing cardiomyocyte apoptosis. The knockdown of SGLT1 also promoted mitochondrial fusion, inhibited mitochondrial fission, and increased ATP content and complex I–IV activity, therefore improving mitochondrial dysfunction and attenuating cardiomyocyte oxidative stress and apoptosis. Inhibition of SGLT1 can reduce cardiomyocyte hypertrophy and oxidative stress caused by intracellular Ca²⁺ overload, and partially decrease the inflammatory response and pyroptosis in cardiomyocytes by suppressing NF-κB and NLRP3/caspase-1 pathway.