Endocrine Abstracts

Objective: Saturated fatty acids (FAs), e.g. stearic acid (SA), induce apoptosis in pancreatic β-cells while unsaturated FAs, e.g. oleic acid (OA) have nearly no detrimental effect. Moreover, unsaturated FAs are capable of inhibiting the pro-apoptotic effect of saturated FAs. Hypoxia is also known to have deleterious effects on β-cell function and viability. In the present study, we have tested the modulatory effect of hypoxia on the effect of FAs on the growth and viability of human pancreatic β-cells NES2Y.

Methods: We used 4% O₂ concentration to generate moderate hypoxia and 1% O₂ concentration to generate strong hypoxia. 20% O₂ concentration was used as normoxia. In experiments, a defined serum-free medium supplemented with 1 mM SA, a combination of 1 mM SA and 0.2 mM OA, or 0.2 mM OA alone bound to a 2% FA-free bovine serum albumin was used.

Results and Conclusions: We showed that hypoxia increased the pro-apoptotic effect of saturated SA. Endoplasmic reticulum stress signalling seemed to be involved in this effect. Hypoxia also decreased the protective effect of unsaturated OA against the pro-apoptotic effect of SA. Thus, in the presence of hypoxia, OA was unable to save SA-treated β-cells from apoptosis induction. Interestingly, hypoxia itself had only weak detrimental effects on NES2Y cells. Our data suggest that hypoxia could represent an important factor in pancreatic β-cell death induced and regulated by FAs and thus in the development of type 2 diabetes mellitus.

This work was supported by research projects PRVOUK P31, PROGRES Q36 from Charles University, Czech Republic, and by grant 18-10144S from the Grant Agency of the Czech Republic.