According to this study, high glucose level in islet cell could increase the release of n-6 PUFA, which acts as endogenous DZNeP purchase ligand for PPAR��. According to our present findings, it is thus possible that the PPAR��-mediated general response of ��-cell to increased glucose level is coupled to the production of unsaturated fatty acids via enzymatic ��6 desaturation. Taken together, these results signify the role of PPAR�� and ��6 fatty acid desaturation in potency of insulin secretion from pancreatic ��-cell.Our findings on PANC-1 cultures incubated with MEK/ERK1/2 inhibitor PD98059 showed no apparent change in ��6D mRNA and protein expression compared to untreated control cells. In contrast with these observations, our results in human hepatoblastoma (HepG2) cells indicated that the expression level of ��6D was significantly increased in the presence of MEK/ERK1/2 inhibitor.

The differences in our results may be due to either a cell-type-specific effect or different sensitivities in methods of measurement and use of relative RT-PCR versus real-time RT-PCR. We also demonstrated that treatment with both ERK1/2 inhibitor and EGFR inhibitor remarkably downregulated GW0742-induced ��6D mRNA and protein expression. In spite of comparable levels of ��6D mRNA expression, EGFR inhibitor had less suppressive effect on PPAR�� agonist-mediated induction of ��6D protein expression than ERK1/2 inhibitor. This difference may be related to additional changes in associated downstream signaling pathways, like PI3K-Akt [22, 23].

So it could be hypothesized that there is increased protein stability or decreased protein degradation in response to inhibition of PI3K, which is downstream of EGFR. Slowed EGF-induced protein degradation following inhibition of PI3K signaling has previously been reported [24].To the best of our knowledge, this study is the first study to examine the combined effect of PPAR�� agonist and ERK1/2 blockade on the gene and protein expression of fatty acid ��6D. We used PANC-1 pancreatic tumor cells which are well-characterized human-derived cells for studying human pancreatic cells in vitro [25]. Based on our result, we could conclude that EGFR signaling pathways maybe involved in the suppression of ��6D expression; however, the relationship between this pathway and PPAR�� remains to be investigated. 5.

ConclusionsOur study showed that PPAR�� and ERK1/2 MAPK signaling pathways affect the gene expression of ��6D in pancreatic carcinoma cell line PANC-1. Furthermore, a possible inhibitory effect Entinostat of ERK1/2 MAPK signaling on PPAR�� activity may serve to coordinate ��6 desaturation of fatty acids in pancreatic cells.Conflict of InterestsThe authors declare that there is no conflict of interests regarding the publication of this paper.AcknowledgmentsThis study was financially supported by grants from the Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Iran.