Effects of human serum albumin complexed with free fatty acids on cell viability and insulin secretion in the hamster pancreatic β-cell line HIT-T15.

Aims: The effects of human serum albumin (HSA) complexed with various free fatty acids (FFAs) on ß-cells have not been studied in detail. In this study, we examined the effects of HSA and its mutants on FFA-induced cell viability changes and insulin secretion from the hamster pancreatic insulinoma cell line, HIT-TI5.

Main Methods: Cells were exposed to different FFAs in the presence of HSA or its mutants and/or bovine serum albumin (BSA) for 24h. Cell viability, apoptosis, insulin secretion, and unbound FFA (FFA(u)) levels were determined.

Key Findings: In the presence of 0.1mM HSA, palmitate and stearate induced significant cell death at 0.1mM or higher, whereas myristate, palmitoleate, oleate, elaidate, linoleate, linoelaidate, and conjugated linoleate showed minimal changes on cell viability. Furthermore, oleate and linoleate were clearly cytoprotective against palmitate-induced cell death. The apoptosis inhibitors, cyclosporin A (csA) and the caspase inhibitor ZVAD-FMK, did not completely prevent FFA-induced cell death, although ZVAD-FMK blocked apoptosis with no differences in the presence of either HSA or BSA. In addition, insulin secretion from the cells was significantly reduced in the presence of HSA/oleate complexes. We also found differential effects of HSA mutants complexed with FFAs on cell viability.

Significance: In summary, our results showed that saturated FFAs induced more cell death than unsaturated FFAs. Furthermore, modified HSA/FFA interactions caused by mutations of key amino acids involved in the binding of FFA to HSA resulted in changes in cell viability, suggesting a possible role of HSA polymorphism on FFA-induced changes in cellular functions.