Palmitate Induces mRNA Translation and Increases ER Protein Load in Islet β-Cells via Activation of the Mammalian Target of Rapamycin Pathway
Saturated free fatty acids (FFAs) have complex effects on the islet β-cell, acutely promoting adaptive hyperplasia but chronically impairing insulin release. The acute effects of FFAs remain incompletely defined. To elucidate these early molecular events, we incubated mouse β-cells and islets with p...
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| Format: | Online |
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American Diabetes Association
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171659/ |
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pubmed-41716592015-10-01 Palmitate Induces mRNA Translation and Increases ER Protein Load in Islet β-Cells via Activation of the Mammalian Target of Rapamycin Pathway Hatanaka, Masayuki Maier, Bernhard Sims, Emily K. Templin, Andrew T. Kulkarni, Rohit N. Evans-Molina, Carmella Mirmira, Raghavendra G. Islet Studies Saturated free fatty acids (FFAs) have complex effects on the islet β-cell, acutely promoting adaptive hyperplasia but chronically impairing insulin release. The acute effects of FFAs remain incompletely defined. To elucidate these early molecular events, we incubated mouse β-cells and islets with palmitate and then studied mRNA translation by polyribosomal profiling and analyzed signaling pathways by immunoblot analysis. We found that palmitate acutely increases polyribosome occupancy of total RNA, consistent with an increase in mRNA translation. This effect on translation was attributable to activation of mammalian target of rapamycin (mTOR) pathways via L-type Ca2+ channels but was independent of insulin signaling. Longer incubations led to depletion of polyribosome-associated RNA, consistent with activation of the unfolded protein response (UPR). Pharmacologic inhibition of mTOR suppressed both the acute effects of palmitate on mRNA translation and the chronic effects on the UPR. Islets from mice fed a high-fat diet for 7 days showed increases in polyribosome-associated RNA and phosphorylation of S6K, both consistent with activation of mTOR. Our results suggest that palmitate acutely activates mRNA translation and that this increase in protein load contributes to the later UPR. American Diabetes Association 2014-10 2014-09-15 /pmc/articles/PMC4171659/ /pubmed/24834975 http://dx.doi.org/10.2337/db14-0105 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Hatanaka, Masayuki Maier, Bernhard Sims, Emily K. Templin, Andrew T. Kulkarni, Rohit N. Evans-Molina, Carmella Mirmira, Raghavendra G. |
| spellingShingle |
Hatanaka, Masayuki Maier, Bernhard Sims, Emily K. Templin, Andrew T. Kulkarni, Rohit N. Evans-Molina, Carmella Mirmira, Raghavendra G. Palmitate Induces mRNA Translation and Increases ER Protein Load in Islet β-Cells via Activation of the Mammalian Target of Rapamycin Pathway |
| author_facet |
Hatanaka, Masayuki Maier, Bernhard Sims, Emily K. Templin, Andrew T. Kulkarni, Rohit N. Evans-Molina, Carmella Mirmira, Raghavendra G. |
| author_sort |
Hatanaka, Masayuki |
| title |
Palmitate Induces mRNA Translation and Increases ER Protein Load in Islet β-Cells via Activation of the Mammalian Target of Rapamycin Pathway |
| title_short |
Palmitate Induces mRNA Translation and Increases ER Protein Load in Islet β-Cells via Activation of the Mammalian Target of Rapamycin Pathway |
| title_full |
Palmitate Induces mRNA Translation and Increases ER Protein Load in Islet β-Cells via Activation of the Mammalian Target of Rapamycin Pathway |
| title_fullStr |
Palmitate Induces mRNA Translation and Increases ER Protein Load in Islet β-Cells via Activation of the Mammalian Target of Rapamycin Pathway |
| title_full_unstemmed |
Palmitate Induces mRNA Translation and Increases ER Protein Load in Islet β-Cells via Activation of the Mammalian Target of Rapamycin Pathway |
| title_sort |
palmitate induces mrna translation and increases er protein load in islet β-cells via activation of the mammalian target of rapamycin pathway |
| description |
Saturated free fatty acids (FFAs) have complex effects on the islet β-cell, acutely promoting adaptive hyperplasia but chronically impairing insulin release. The acute effects of FFAs remain incompletely defined. To elucidate these early molecular events, we incubated mouse β-cells and islets with palmitate and then studied mRNA translation by polyribosomal profiling and analyzed signaling pathways by immunoblot analysis. We found that palmitate acutely increases polyribosome occupancy of total RNA, consistent with an increase in mRNA translation. This effect on translation was attributable to activation of mammalian target of rapamycin (mTOR) pathways via L-type Ca2+ channels but was independent of insulin signaling. Longer incubations led to depletion of polyribosome-associated RNA, consistent with activation of the unfolded protein response (UPR). Pharmacologic inhibition of mTOR suppressed both the acute effects of palmitate on mRNA translation and the chronic effects on the UPR. Islets from mice fed a high-fat diet for 7 days showed increases in polyribosome-associated RNA and phosphorylation of S6K, both consistent with activation of mTOR. Our results suggest that palmitate acutely activates mRNA translation and that this increase in protein load contributes to the later UPR. |
| publisher |
American Diabetes Association |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171659/ |
| _version_ |
1613136145826185216 |