Effect of Saturated Stearic Acid on MAP Kinase and ER Stress Signaling Pathways during Apoptosis Induction in Human Pancreatic β-Cells Is Inhibited by Unsaturated Oleic Acid

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.

Gain-of-Function Mutations of SLC16A11 Contribute to the Pathogenesis of Type 2 Diabetes

“…HepG2 cells incubated with or without sodium stearate. Sodium stearate represents one of the key saturated fatty acids presented in HFD and is able to significantly activate ER-stresssignaling pathways usually associated with fatty liver diseases and diabetes ( Srá mek et al, 2017). Consistent with findings in animals, overexpression of the human mutant SLC16A11 caused more triglyceride accumulation compared to cells transfected with the wild-type SLC16A11 or empty vector in HepG2 cells ( Figure 3H).…”

Hypoxia Modulates Effects of Fatty Acids on NES2Y Human Pancreatic β-cells

“…Our previous studies showed that SA, at a concentration of 1 mM, induces endoplasmic reticulum stress and apoptosis in most NES2Y cells within 24 h of application [4,35,36,37]. Therefore, all assessments were performed within 24 h after FAs application except for the assessment of cell growth and viability.…”

Na dobre i na złe – czyli rola oddziaływania trzustki, śródbłonka i tkanki tłuszczowej w regulacji funkcjonowania komórek β i rozwoju cukrzycy typu 2 związanej z otyłością

“…The chronic treatment of β-cells with unsaturated FAs, such as oleate, palmitoleate, and arachidonate, increased GSIS and the proliferation and survival of β-cells, and counteracted the lipotoxic effects of palmitate in rodent BRIN-BD11, INS-1E, MIN6 cell lines and human NES2Y pancreatic β-cell lines and islets, respectively [50][51][52][53]. Endocannabinoids (arachidonate derivatives) were shown to stimulate insulin secretion in INS-1E cells through cytoskeletal reorganization [54].…”