Abstract
Saturated fatty acids (FAs) induce apoptosis in the human pancreatic NES2Y β-cell line while unsaturated FAs 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-cells 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 the human pancreatic NES2Y β-cells. This study represents the first study testing hypoxia effect on effects of FAs in pancreatic β-cells as well as in other cell types. We showed that hypoxia increased the pro-apoptotic effect of saturated stearic acid (SA). Endoplasmic reticulum stress signaling seemed to be involved while redistribution of FA transporters fatty acid translocase/cluster of differentiation 36 (FAT/CD36) and fatty acid-binding protein (FABP) do not seem to be involved in this effect. Hypoxia also strongly decreased the protective effect of unsaturated oleic acid (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. Hypoxia itself had only a weak detrimental effect 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.
Highlights
It was suggested that increased levels of fatty acids (FAs) in the blood are factors contributing to the failure and death of pancreatic β-cells
Hypoxia itself had only a weak detrimental effect on NES2Y cells. These results suggest that hypoxia could represent an important factor in pancreatic β-cell death induced and regulated by FAs and in the development of type 2 diabetes mellitus (T2DM)
The effect of strong hypoxia was markedly stronger than the effect of moderate hypoxia (Figure 1A)
Summary
It was suggested that increased levels of fatty acids (FAs) in the blood are factors contributing to the failure and death of pancreatic β-cells. ATF6 after its activation by cleavage translocates to the nucleus where it functions as a transcription factor These pathways primarily participate in the restoration of ER homeostasis, e.g., by increasing the expression of chaperones, such as immunoglobulin heavy chain-binding protein (BiP) [16]. It was documented in cardiac myocytes that strong hypoxia induces the redistribution of two FAs transporters, fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and fatty acid-binding protein (FABP), from the intracellular pool to the plasma membrane It leads to increased FAs accumulation [18]. Hypoxia itself had only a weak detrimental effect on NES2Y cells These results suggest that hypoxia could represent an important factor in pancreatic β-cell death induced and regulated by FAs and in the development of T2DM
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