Knockdown of SGLT1 prevents the apoptosis of cardiomyocytes induced by glucose fluctuation via relieving oxidative stress and mitochondrial dysfunction.

Abstract

Fluctuations in the concentration of glucose in the blood is more detrimental than a constantly high level of glucose with respect to the development of cardiovascular complications associated with diabetes mellitus (DM). Sodium glucose cotransporter 2 (SGLT2) inhibitors have been developed as antidiabetic drugs with cardiovascular benefits; however, whether inhibition of SGLT1 protects the diabetic heart remains to be determined. This study investigated the role of SGLT1 in rat H9c2 cardiomyocytes subjected to fluctuating levels of glucose and the underlying mechanisms. The results indicated that knockdown of SGLT1 restored cell proliferation and suppressed the cytotoxicity associated with fluctuating glucose levels. Oxidative stress was induced in H9c2 cells subjected to fluctuating glucose levels, but these changes were effectively reversed by knockdown of SGLT1, as manifested by reductions in the level of intracellular reactive oxygen species and increased antioxidant activity. Further study demonstrated that knockdown of SGLT1 attenuated the mitochondrial dysfunction in H9c2 cells exposed to fluctuating glucose levels, by restoring mitochondrial membrane potential and promoting mitochondrial fusion. In addition, knockdown of SGLT1 downregulated the expression of Bax, upregulated the expression of Bcl-2, and reduced the activation of caspase-3 in H9c2 cells subjected to fluctuating levels of glucose. Collectively, our results show that knockdown of SGLT1 ameliorates the apoptosis of cardiomyocyte caused by fluctuating glucose levels via regulating oxidative stress and combatting mitochondrial dysfunction.

• Authors: Qian Chai, Jiajing Miao, Meili Liu, Ziying Zhang, Ziang Meng, Weihua Wu
• Journal: Biochemistry and cell biology = Biochimie et biologie cellulaire (Biochem Cell Biol) Vol. 99 Issue 3 Pg. 356-363 (06 2021) ISSN: 1208-6002 [Electronic] Canada
• PMID: 33259229 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• Slc5a1 protein, rat
• Sodium-Glucose Transporter 1
• Glucose

Topics

• Animals
• Apoptosis
• Glucose (pharmacology)
• Membrane Potential, Mitochondrial
• Mitochondria (drug effects, metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Oxidative Stress (drug effects)
• Rats
• Reactive Oxygen Species (metabolism)
• Sodium-Glucose Transporter 1 (antagonists & inhibitors, genetics, metabolism)