%0 Journal Article %A Krizhanovskii, Camilla %A G. Fred, Rikard %A Oskarsson, Marie E. %A Westermark, Gunilla T. %A Welsh, Nils %D 2017 %T Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-βH1 cells %U https://tandf.figshare.com/articles/journal_contribution/Addition_of_exogenous_sodium_palmitate_increases_the_IAPP_insulin_mRNA_ratio_via_GPR40_in_human_EndoC-_H1_cells/5472907 %R 10.6084/m9.figshare.5472907.v1 %2 https://ndownloader.figshare.com/files/9465235 %K Amyloid %K fatty acids %K insulin %K islet amyloid polypeptide (IAPP) %K palmitate %X

Background: Enhanced IAPP production may contribute to islet amyloid formation in type 2 diabetes. The objective of this study was to determine the effects of the saturated fatty acid palmitate on IAPP levels in human β-cells.

Methods: EndoC-βH1 cells and human islets were cultured in the presence of sodium palmitate. Effects on IAPP/insulin mRNA expression and secretion were determined using real-time qPCR/ELISA. Pharmacological activators and/or inhibitors and RNAi were used to determine the underlying mechanisms.

Results: We observed that EndoC-βH1 cells exposed to palmitate for 72 h displayed decreased expression of Pdx-1 and MafA and increased expression of thioredoxin-interacting protein (TXNIP), reduced insulin mRNA expression and glucose-induced insulin secretion, as well as increased IAPP mRNA expression and secretion. Further, these effects were independent of fatty acid oxidation, but abolished in response to GPR40 inhibition/downregulation. In human islets both a high glucose concentration and palmitate promoted increased IAPP mRNA levels, resulting in an augmented IAPP/insulin mRNA ratio. This was paralleled by elevated IAPP/insulin protein secretion and content ratios.

Conclusions: Addition of exogenous palmitate to human β-cells increased the IAPP/insulin expression ratio, an effect contributed to by activation of GPR40. These findings may be pertinent to our understanding of the islet amyloid formation process.

%I Taylor & Francis