Conclusions
Increased hepassocin secretion in hyperglycemic crisis might offset the deleterious effects of hyperglycemia on hepatocytes.
Objective
To investigate the possible hepatic protection effects of hepassocin in hyperglycemic crisis. Design, setting, and patients: Plasma hepassocin concentrations and routine biochemistry were measured in 21 patients with hyperglycemic crisis before and after standard treatments. The effects of hepassocin on hepatic functions were evaluated in streptozotocin-induced hyperglycemic mice (STZ mice). HepG2 cells were used to clarify the possible mechanisms regulating hepassocin expression.
Results
Plasma hepassocin concentrations decreased significantly in subjects with hyperglycemic crisis after standard treatment accompanied by improved hepatic functions. Correction of hyperglycemia in STZ mice also decreased the hepatic hepassocin expression. Injection of recombinant hepassocin improved hepatic functions and histologic changes and increased the expression of antioxidative stress proteins, including superoxide dismutase 1 (SOD1). In HepG2 cells, high glucose increased hepassocin expression through signal transducer and activator of transcription 3 and hepatocyte nuclear factor-related pathways. We also demonstrated that hepassocin increased SOD1 expression through an extracellular signal-regulated kinase 1/2 nuclear factor erythroid-2-related factor 2 pathway, decreasing ethyl acetate-induced ROS production and improving cell viability. Conclusions: Increased hepassocin secretion in hyperglycemic crisis might offset the deleterious effects of hyperglycemia on hepatocytes.