Abstract
It has been shown that saturated fatty acids (FAs) have a detrimental effect on pancreatic β-cells function and survival, leading to apoptosis, whereas unsaturated FAs are well tolerated and are even capable of inhibiting the pro-apoptotic effect of saturated FAs. Molecular mechanisms of apoptosis induction and regulation by FAs in β-cells remain unclear; however, mitogen-activated protein (MAP) kinase and endoplasmic reticulum (ER) stress signaling pathways may be involved. In this study, we tested how unsaturated oleic acid (OA) affects the effect of saturated stearic acid (SA) on the p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) pathways as well as the ER stress signaling pathways during apoptosis induction in the human pancreatic β-cells NES2Y. We demonstrated that OA is able to inhibit all effects of SA. OA alone has only minimal or no effects on tested signaling in NES2Y cells. The point of OA inhibitory intervention in SA-induced apoptotic signaling thus seems to be located upstream of the discussed signaling pathways.
Highlights
Increased levels of fatty acids (FAs) in blood are considered to be one of the main factors responsible for pancreatic β-cell death in type 2 diabetes [1,2,3,4,5]
We showed that oleic acid (OA) (0.2 mM) inhibited stearic acid (SA)-induced (1 mM) cell death of NES2Y cells
As well as other authors, have shown that unsaturated FAs have nearly no detrimental effect on pancreatic β-cells, but that they are capable of inhibiting the pro-apoptotic effect of saturated FAs [2,4,5,6,7,8]
Summary
Increased levels of fatty acids (FAs) in blood are considered to be one of the main factors responsible for pancreatic β-cell death in type 2 diabetes [1,2,3,4,5]. It was shown that apoptosis induced by saturated FAs can be mediated by p38 MAPK (mitogen-activated protein kinase) and ERK (extracellular signal-regulated kinases) MAPK signaling pathways [10,11,12,13,14] as well as by endoplasmic reticulum (ER) stress signaling [15,16]. P38 MAPK regulates the activity of MAPKAPK-2 (MAPK-activated protein kinase 2) which is involved in nuclear export of activated p38 MAPK [18] It may affect the activation of some proteins such as NF-κB (nuclear factor kappa B) [19] or caspase-3 [20]. These proteins are involved in the regulation of apoptosis induction
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