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

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.