Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-βH1 cells
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 o...
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| Format: | Article |
| Language: | English |
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Upsala Medical Society
2017-07-01
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| Series: | Upsala Journal of Medical Sciences |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/03009734.2017.1368745 |
| _version_ | 1797728829700046848 |
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| author | Camilla Krizhanovskii Rikard G. Fred Marie E. Oskarsson Gunilla T. Westermark Nils Welsh |
| author_facet | Camilla Krizhanovskii Rikard G. Fred Marie E. Oskarsson Gunilla T. Westermark Nils Welsh |
| author_sort | Camilla Krizhanovskii |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T11:19:46Z |
| format | Article |
| id | doaj.art-751f7d8d553644e18cb9885e22949afe |
| institution | Directory Open Access Journal |
| issn | 0300-9734 2000-1967 |
| language | English |
| last_indexed | 2024-03-12T11:19:46Z |
| publishDate | 2017-07-01 |
| publisher | Upsala Medical Society |
| record_format | Article |
| series | Upsala Journal of Medical Sciences |
| spelling | doaj.art-751f7d8d553644e18cb9885e22949afe2023-09-02T01:00:51ZengUpsala Medical SocietyUpsala Journal of Medical Sciences0300-97342000-19672017-07-01122314915910.1080/03009734.2017.13687451368745Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-βH1 cellsCamilla Krizhanovskii0Rikard G. Fred1Marie E. Oskarsson2Gunilla T. Westermark3Nils Welsh4Uppsala UniversityUppsala UniversityUppsala UniversityUppsala UniversityUppsala UniversityBackground: 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.http://dx.doi.org/10.1080/03009734.2017.1368745Amyloidfatty acidsinsulinislet amyloid polypeptide (IAPP)palmitate |
| spellingShingle | Camilla Krizhanovskii Rikard G. Fred Marie E. Oskarsson Gunilla T. Westermark Nils Welsh Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-βH1 cells Upsala Journal of Medical Sciences Amyloid fatty acids insulin islet amyloid polypeptide (IAPP) palmitate |
| title | Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-βH1 cells |
| title_full | Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-βH1 cells |
| title_fullStr | Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-βH1 cells |
| title_full_unstemmed | Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-βH1 cells |
| title_short | Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-βH1 cells |
| title_sort | addition of exogenous sodium palmitate increases the iapp insulin mrna ratio via gpr40 in human endoc βh1 cells |
| topic | Amyloid fatty acids insulin islet amyloid polypeptide (IAPP) palmitate |
| url | http://dx.doi.org/10.1080/03009734.2017.1368745 |
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