Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
Journal website http://www.jocmr.org

Letter to the Editor

Volume 11, Number 11, November 2019, pages 769-772

The Possible Mechanisms for Improvement of Liver Function due to Sodium-Glucose Cotransporter-2 Inhibitors

Figure

Figure 1.
Figure 1. The possible underlying mechanisms for an improvement of liver function due to SGLT2is. ACC: acetyl-CoA carboxylase; AMPK: adenosine 5'-monophosphate-activated protein kinase; FA: fatty acid; SGLT2is: sodium-glucose cotransporter-2 inhibitors; TG: triglyceride; AMP: adenosine 5'-monophosphate; ATP: adenosine triphosphate.

Table

Table 1. Reported Mechanisms for an Improvement of Liver Function due to SGLT2is
 
SGLT2isReferencesSubjectsEffects on liver and putative mechanisms to improve liver function
SGLT2is: sodium-glucose cotransporter-2 inhibitors; ACC: acetyl-CoA carboxylase; AMPK: adenosine 5'-monophosphate-activated protein kinase; NAFLD: nonalcoholic fatty liver disease; HEK: human embryonic kidney.
Ipragliflozin[5]Type 2 diabetic miceImprovement of hepatic steatosis and liver injury; reduction of plasma and liver levels of oxidative stress biomarkers and inflammatory markers
Ipragliflozin[6]Type 1 diabetic ratsImprovement of hepatic steatosis and liver injury; reduction of liver levels of oxidative stress biomarkers and plasma levels of inflammatory markers
Ipragliflozin[7]NAFLD ratsPrevention of hepatic triglyceride accumulation, large lipid droplet formation and liver fibrosis
Ipragliflozin[8]Obese micePrevention of ectopic fat accumulation in the liver
Luseogliflozin[9, 10]Type 2 diabetic patients with NAFLDReduction of hepatic fat content
Empagliflozin[11]Well-controlled type 2 diabetic patientsLowering of liver fat content
Canagliflozin[12]HEK-293 cellsAMPK activation by inhibition of Complex I of the respiratory chain; inhibition of lipid synthesis, by phosphorylation of ACC at the AMPK sites in human hepatocytes, which leads to downregulation of fatty acid synthesis-related molecules and upregulation of β oxidation-associated molecules
Tofogliflozin[13]C57BL/6 miceDecrease of hepatic triglyceride content; acceleration of lipolysis in adipose tissue and hepatic β-oxidation