Caffeic acid does not protect human pancreatic β cells against stearic acid‐induced ER stress and apoptosis

Abstract

Long‐term elevation of saturated fatty acids in blood has a deleterious effect on pancreatic β‐cell function and survival, leading to endoplasmic reticulum (ER) stress and apoptosis. This fundamentally contributes to type 2 diabetes development. Caffeic acid (CA) was found to protect various cell types against several proapoptotic stimuli, including fatty acids. However, its potential protective effect against fatty acid‐induced apoptosis was not ascertained in pancreatic β cells yet. Therefore, the objective of this study was to examine this in the human pancreatic β‐cell lines NES2Y and 1.1B4. In both cell lines, CA did not modify the effect of saturated stearic acid (SA) on β‐cell growth and viability. At higher concentrations, CA significantly even intensified the adverse effect of SA. Consistent with this, CA did not exhibit any inhibitory effect on SA‐induced markers of ongoing apoptosis as well as ER stress. At higher concentrations, CA again slightly potentiated the effect of SA. CA applied alone was well tolerated up to 1 mM; however, at higher concentrations, it had detrimental effects in both cell lines. To conclude, we have shown that the treatment with caffeic acid has no inhibitory effect on SA‐induced ER stress and apoptosis in the human pancreatic β cells. Moreover, at higher concentrations, CA has proapoptotic potential.Practical applications: Caffeic acid exhibits a protective effect against saturated fatty acids in human hepatocytes. However, our data obtained with human β‐cell lines suggest that the potential usage of caffeic acid as a dietary component for the prevention and treatment of type 2 diabetes mellitus, developed with the contribution of saturated fatty acid‐induced apoptosis of β cells, seems rather unlikely.