Activation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) by free fatty acid receptor 1 (FFAR1/GPR40) protects from palmitate-induced beta cell death, but plays no role in insulin secretion

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Madhura PanseSusanne Ullrich

Abstract

GPR40/FFAR1 mediates palmitate-induced stimulation of insulin secretion but its involvement in lipotoxicity is controversial. Our previous observations suggest that FFAR1/GPR40 agonists protect against lipotoxicity although the underlying mechanism remains elusive. The present study examines the role of ERK1/2 and GPR40/FFAR1 in palmitate-induced stimulation of insulin secretion and beta cell death. Insulin secretion of INS-1E cells was measured by radioimmunoassay. Protein phosphorylation was examined on Western blots. Apoptosis was assessed by TUNEL staining. Palmitate and the GPR40/FFAR1 agonist TUG-469 increased phosphorylation of ERK1/2 at low (2.8 mmol/L) and high (12 mmol/L) glucose but stimulated insulin secretion only at high glucose. The MEK1 inhibitor PD98059 significantly reduced phosphorylation of ERK1/2 but did not reverse the stimulation of secretion induced by glucose, palmitate or TUG-469. PD98059 rather augmented glucose-induced secretion. Prolonged exposure to palmitate stimulated apoptosis, an effect counteracted by TUG-469. PD98059 accentuated palmitate-induced apoptosis and reversed TUG-469-mediated inhibition of cell death. Activation of ERK1/2 by palmitate and GPR40/FFAR1 agonist correlates neither with ...Continue Reading

Citations

Jun 15, 2016·Chemical Reviews·Graeme MilliganBrian D Hudson
Feb 13, 2017·Progress in Neurobiology·Rafael FrancoMarta Zamarbide
Jun 23, 2018·The Journal of Clinical Endocrinology and Metabolism·Laura StirmHarald Staiger
Jan 24, 2019·The Journal of Biological Chemistry·Emily S MichaelAthan Kuliopulos
Nov 28, 2019·Expert Opinion on Therapeutic Patents·Zheng LiLuyong Zhang
Oct 27, 2018·Frontiers in Endocrinology·Silvano Paternoster, Marco Falasca
Feb 14, 2021·International Journal of Molecular Sciences·Manuel GrundmannFrank Eitner
May 1, 2021·International Journal of Molecular Sciences·Jan ŠrámekJan Kovář
Aug 28, 2021·International Journal of Molecular Sciences·C J Urso, Heping Zhou

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