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Biosynthetic Activity Differs Between Islet Cell Types and in Beta Cells Is Modulated by Glucose and Not by Secretion

A correct biosynthetic activity is thought to be essential for the long-term function and survival of islet cells in culture and possibly also after islet transplantation. Compared to the secretory activity, biosynthetic activity has been poorly studied in pancreatic islet cells. Here we aimed to as...

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Autores principales: Cottet-Dumoulin, David, Lavallard, Vanessa, Lebreton, Fanny, Wassmer, Charles H, Bellofatto, Kevin, Parnaud, Géraldine, Berishvili, Ekaterine, Berney, Thierry, Bosco, Domenico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940959/
https://www.ncbi.nlm.nih.gov/pubmed/33367617
http://dx.doi.org/10.1210/endocr/bqaa239
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author Cottet-Dumoulin, David
Lavallard, Vanessa
Lebreton, Fanny
Wassmer, Charles H
Bellofatto, Kevin
Parnaud, Géraldine
Berishvili, Ekaterine
Berney, Thierry
Bosco, Domenico
author_facet Cottet-Dumoulin, David
Lavallard, Vanessa
Lebreton, Fanny
Wassmer, Charles H
Bellofatto, Kevin
Parnaud, Géraldine
Berishvili, Ekaterine
Berney, Thierry
Bosco, Domenico
author_sort Cottet-Dumoulin, David
collection PubMed
description A correct biosynthetic activity is thought to be essential for the long-term function and survival of islet cells in culture and possibly also after islet transplantation. Compared to the secretory activity, biosynthetic activity has been poorly studied in pancreatic islet cells. Here we aimed to assess biosynthetic activity at the single cell level to investigate if protein synthesis is dependent on secretagogues and increased as a consequence of hormonal secretion. Biosynthetic activity in rat islet cells was studied at the single cell level using O-propargyl-puromycin (OPP) that incorporates into newly translated proteins and chemically ligates to a fluorescent dye by “click” reaction. Heterogeneous biosynthetic activity was observed between the four islet cell types, with delta cells showing the higher relative protein biosynthesis. Beta cells protein biosynthesis was increased in response to glucose while 3-isobutyl-1-methylxanthine and phorbol-12-myristate-13-acetate, 2 drugs known to stimulate insulin secretion, had no similar effect on protein biosynthesis. However, after several hours of secretion, protein biosynthesis remained high even when cells were challenged to basal conditions. These results suggest that mechanisms regulating secretion and biosynthesis in islet cells are different, with glucose directly triggering beta cells protein biosynthesis, independently of insulin secretion. Furthermore, this OPP labeling approach is a promising method to identify newly synthesized proteins under various physiological and pathological conditions.
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spelling pubmed-79409592021-03-15 Biosynthetic Activity Differs Between Islet Cell Types and in Beta Cells Is Modulated by Glucose and Not by Secretion Cottet-Dumoulin, David Lavallard, Vanessa Lebreton, Fanny Wassmer, Charles H Bellofatto, Kevin Parnaud, Géraldine Berishvili, Ekaterine Berney, Thierry Bosco, Domenico Endocrinology Research Articles A correct biosynthetic activity is thought to be essential for the long-term function and survival of islet cells in culture and possibly also after islet transplantation. Compared to the secretory activity, biosynthetic activity has been poorly studied in pancreatic islet cells. Here we aimed to assess biosynthetic activity at the single cell level to investigate if protein synthesis is dependent on secretagogues and increased as a consequence of hormonal secretion. Biosynthetic activity in rat islet cells was studied at the single cell level using O-propargyl-puromycin (OPP) that incorporates into newly translated proteins and chemically ligates to a fluorescent dye by “click” reaction. Heterogeneous biosynthetic activity was observed between the four islet cell types, with delta cells showing the higher relative protein biosynthesis. Beta cells protein biosynthesis was increased in response to glucose while 3-isobutyl-1-methylxanthine and phorbol-12-myristate-13-acetate, 2 drugs known to stimulate insulin secretion, had no similar effect on protein biosynthesis. However, after several hours of secretion, protein biosynthesis remained high even when cells were challenged to basal conditions. These results suggest that mechanisms regulating secretion and biosynthesis in islet cells are different, with glucose directly triggering beta cells protein biosynthesis, independently of insulin secretion. Furthermore, this OPP labeling approach is a promising method to identify newly synthesized proteins under various physiological and pathological conditions. Oxford University Press 2020-12-25 /pmc/articles/PMC7940959/ /pubmed/33367617 http://dx.doi.org/10.1210/endocr/bqaa239 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Cottet-Dumoulin, David
Lavallard, Vanessa
Lebreton, Fanny
Wassmer, Charles H
Bellofatto, Kevin
Parnaud, Géraldine
Berishvili, Ekaterine
Berney, Thierry
Bosco, Domenico
Biosynthetic Activity Differs Between Islet Cell Types and in Beta Cells Is Modulated by Glucose and Not by Secretion
title Biosynthetic Activity Differs Between Islet Cell Types and in Beta Cells Is Modulated by Glucose and Not by Secretion
title_full Biosynthetic Activity Differs Between Islet Cell Types and in Beta Cells Is Modulated by Glucose and Not by Secretion
title_fullStr Biosynthetic Activity Differs Between Islet Cell Types and in Beta Cells Is Modulated by Glucose and Not by Secretion
title_full_unstemmed Biosynthetic Activity Differs Between Islet Cell Types and in Beta Cells Is Modulated by Glucose and Not by Secretion
title_short Biosynthetic Activity Differs Between Islet Cell Types and in Beta Cells Is Modulated by Glucose and Not by Secretion
title_sort biosynthetic activity differs between islet cell types and in beta cells is modulated by glucose and not by secretion
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940959/
https://www.ncbi.nlm.nih.gov/pubmed/33367617
http://dx.doi.org/10.1210/endocr/bqaa239
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