The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass

Abstract Mechanistic target of rapamycin complex 1 (mTORC1) deficiency or chronic hyperactivation in pancreatic β-cells leads to diabetes. mTORC1 complexes with La-related protein 1 (LARP1) to specifically regulate the expression of 5′ terminal oligopyrimidine tract (5′TOP) mRNAs which encode protei...

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Autores principales:	Joao Pedro Werneck-de-Castro, Flavia Leticia Martins Peçanha, Diego Henrique Silvestre, Ernesto Bernal-Mizrachi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f414533262e4418686e776c61f76aed1
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spelling	oai:doaj.org-article:f414533262e4418686e776c61f76aed12021-12-02T15:23:38ZThe RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass10.1038/s41598-021-81457-42045-2322https://doaj.org/article/f414533262e4418686e776c61f76aed12021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81457-4https://doaj.org/toc/2045-2322Abstract Mechanistic target of rapamycin complex 1 (mTORC1) deficiency or chronic hyperactivation in pancreatic β-cells leads to diabetes. mTORC1 complexes with La-related protein 1 (LARP1) to specifically regulate the expression of 5′ terminal oligopyrimidine tract (5′TOP) mRNAs which encode proteins of the translation machinery and ribosome biogenesis. Here we show that LARP1 is the most expressed LARP in mouse islets and human β-cells, being 2–4-fold more abundant than LARP1B, a member of the family that also interacts with mTORC1. Interestingly, β-cells from diabetic patients have higher LARP1 and LARP1B expression. However, specific deletion of Larp1 gene in β-cells (β-Larp1KO mice) did not impair insulin secretion and glucose metabolism in male and female mice. High fat or high branched-chain amino acid (BCAA) diets did not disturb glucose homeostasis compared to control littermates up to 8 weeks; BCAA diet slightly impaired glucose tolerance in the β-Larp1KO mice at 16 weeks. However, no differences in plasma insulin levels, non-fasting glycemia and β-cell mass were observed in the β-Larp1KO mice. In conclusion, LARP1 is the most abundant LARP in mouse islets and human β-cells, and it is upregulated in diabetic subjects. However, genetically disruption of Larp1 gene did not impact glucose homeostasis in basal and diabetogenic conditions, suggesting no major role for LARP1 in β-cells.Joao Pedro Werneck-de-CastroFlavia Leticia Martins PeçanhaDiego Henrique SilvestreErnesto Bernal-MizrachiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joao Pedro Werneck-de-Castro Flavia Leticia Martins Peçanha Diego Henrique Silvestre Ernesto Bernal-Mizrachi The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass
description	Abstract Mechanistic target of rapamycin complex 1 (mTORC1) deficiency or chronic hyperactivation in pancreatic β-cells leads to diabetes. mTORC1 complexes with La-related protein 1 (LARP1) to specifically regulate the expression of 5′ terminal oligopyrimidine tract (5′TOP) mRNAs which encode proteins of the translation machinery and ribosome biogenesis. Here we show that LARP1 is the most expressed LARP in mouse islets and human β-cells, being 2–4-fold more abundant than LARP1B, a member of the family that also interacts with mTORC1. Interestingly, β-cells from diabetic patients have higher LARP1 and LARP1B expression. However, specific deletion of Larp1 gene in β-cells (β-Larp1KO mice) did not impair insulin secretion and glucose metabolism in male and female mice. High fat or high branched-chain amino acid (BCAA) diets did not disturb glucose homeostasis compared to control littermates up to 8 weeks; BCAA diet slightly impaired glucose tolerance in the β-Larp1KO mice at 16 weeks. However, no differences in plasma insulin levels, non-fasting glycemia and β-cell mass were observed in the β-Larp1KO mice. In conclusion, LARP1 is the most abundant LARP in mouse islets and human β-cells, and it is upregulated in diabetic subjects. However, genetically disruption of Larp1 gene did not impact glucose homeostasis in basal and diabetogenic conditions, suggesting no major role for LARP1 in β-cells.
format	article
author	Joao Pedro Werneck-de-Castro Flavia Leticia Martins Peçanha Diego Henrique Silvestre Ernesto Bernal-Mizrachi
author_facet	Joao Pedro Werneck-de-Castro Flavia Leticia Martins Peçanha Diego Henrique Silvestre Ernesto Bernal-Mizrachi
author_sort	Joao Pedro Werneck-de-Castro
title	The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass
title_short	The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass
title_full	The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass
title_fullStr	The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass
title_full_unstemmed	The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass
title_sort	rna-binding protein larp1 is dispensable for pancreatic β-cell function and mass
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f414533262e4418686e776c61f76aed1
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The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass

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