Mechanisms of apoptosis induction and inhibition by fatty acids in pancreatic β-cells

Recently, diabetes mellitus type 2 (DMT2) represents one of the most important metabolic diseases according to its incidence and economic impacts. One of the main reasons of this diesease is loss of function and viability of pancreatic β-cells due to the effect of increased levels of saturated fatty acids (FAs). Unsaturated FAs are better tolerated by β-cells. They are even capable of inhibiting detrimental effects of saturated FAs. Molecular mechanisms of apoptosis induction in pancreatic β-cells by saturated FAs as well as mechanisms of inhibition of this induction by unsaturated FAs are not completely elucidated. The main aim of this study was to contribute to elucidation of these mechanisms. Concerning human pancreatic β-cell line NES2Y we demonstarted: (1) Activation of caspase-2 by stearic acid (SA), in apoptosis inducing concentration (1 mM), is not crucial for the process of apoptosis induction. However, this caspase modulates SA-induced endoplasmic reticulum (ER) stress pathways. (2) SA (1 mM) activates the p38 MAPK signaling pathway and inhibits the ERK signaling pathway. Inhibition of the ERK signaling pathway is probably a consequance of the p38 MAPK pathway activation. However, p38 MAPK is not very likely crutial for the apoptosis induction by SA. Unsaturated oleic acid (OA, 0.2 mM) is able to..