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The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1

[Image: see text] To characterize the impact of metabolic disease on the peptidome of human and mouse pancreatic islets, LC-MS was used to analyze extracts of human and mouse islets, purified mouse alpha, beta, and delta cells, supernatants from mouse islet incubations, and plasma from patients with...

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Autores principales: Galvin, Sam G., Kay, Richard G., Foreman, Rachel, Larraufie, Pierre, Meek, Claire L., Biggs, Emma, Ravn, Peter, Jermutus, Lutz, Reimann, Frank, Gribble, Fiona M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419866/
https://www.ncbi.nlm.nih.gov/pubmed/34423991
http://dx.doi.org/10.1021/acs.jproteome.1c00463
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author Galvin, Sam G.
Kay, Richard G.
Foreman, Rachel
Larraufie, Pierre
Meek, Claire L.
Biggs, Emma
Ravn, Peter
Jermutus, Lutz
Reimann, Frank
Gribble, Fiona M.
author_facet Galvin, Sam G.
Kay, Richard G.
Foreman, Rachel
Larraufie, Pierre
Meek, Claire L.
Biggs, Emma
Ravn, Peter
Jermutus, Lutz
Reimann, Frank
Gribble, Fiona M.
author_sort Galvin, Sam G.
collection PubMed
description [Image: see text] To characterize the impact of metabolic disease on the peptidome of human and mouse pancreatic islets, LC-MS was used to analyze extracts of human and mouse islets, purified mouse alpha, beta, and delta cells, supernatants from mouse islet incubations, and plasma from patients with type 2 diabetes. Islets were obtained from healthy and type 2 diabetic human donors, and mice on chow or high fat diet. All major islet hormones were detected in lysed islets as well as numerous peptides from vesicular proteins including granins and processing enzymes. Glucose-dependent insulinotropic peptide (GIP) was not detectable. High fat diet modestly increased islet content of proinsulin-derived peptides in mice. Human diabetic islets contained increased content of proglucagon-derived peptides at the expense of insulin, but no evident prohormone processing defects. Diabetic plasma, however, contained increased ratios of proinsulin and des-31,32-proinsulin to insulin. Active GLP-1 was detectable in human and mouse islets but 100–1000-fold less abundant than glucagon. LC-MS offers advantages over antibody-based approaches for identifying exact peptide sequences, and revealed a shift toward islet insulin production in high fat fed mice, and toward proglucagon production in type 2 diabetes, with no evidence of systematic defective prohormone processing.
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spelling pubmed-84198662021-09-07 The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1 Galvin, Sam G. Kay, Richard G. Foreman, Rachel Larraufie, Pierre Meek, Claire L. Biggs, Emma Ravn, Peter Jermutus, Lutz Reimann, Frank Gribble, Fiona M. J Proteome Res [Image: see text] To characterize the impact of metabolic disease on the peptidome of human and mouse pancreatic islets, LC-MS was used to analyze extracts of human and mouse islets, purified mouse alpha, beta, and delta cells, supernatants from mouse islet incubations, and plasma from patients with type 2 diabetes. Islets were obtained from healthy and type 2 diabetic human donors, and mice on chow or high fat diet. All major islet hormones were detected in lysed islets as well as numerous peptides from vesicular proteins including granins and processing enzymes. Glucose-dependent insulinotropic peptide (GIP) was not detectable. High fat diet modestly increased islet content of proinsulin-derived peptides in mice. Human diabetic islets contained increased content of proglucagon-derived peptides at the expense of insulin, but no evident prohormone processing defects. Diabetic plasma, however, contained increased ratios of proinsulin and des-31,32-proinsulin to insulin. Active GLP-1 was detectable in human and mouse islets but 100–1000-fold less abundant than glucagon. LC-MS offers advantages over antibody-based approaches for identifying exact peptide sequences, and revealed a shift toward islet insulin production in high fat fed mice, and toward proglucagon production in type 2 diabetes, with no evidence of systematic defective prohormone processing. American Chemical Society 2021-08-23 2021-09-03 /pmc/articles/PMC8419866/ /pubmed/34423991 http://dx.doi.org/10.1021/acs.jproteome.1c00463 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Galvin, Sam G.
Kay, Richard G.
Foreman, Rachel
Larraufie, Pierre
Meek, Claire L.
Biggs, Emma
Ravn, Peter
Jermutus, Lutz
Reimann, Frank
Gribble, Fiona M.
The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1
title The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1
title_full The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1
title_fullStr The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1
title_full_unstemmed The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1
title_short The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1
title_sort human and mouse islet peptidome: effects of obesity and type 2 diabetes, and assessment of intraislet production of glucagon-like peptide-1
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419866/
https://www.ncbi.nlm.nih.gov/pubmed/34423991
http://dx.doi.org/10.1021/acs.jproteome.1c00463
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