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Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse

Cystathionine beta synthase (CBS) catalyzes the first step of the transsulfuration pathway from homocysteine to cystathionine, and its deficiency leads to hyperhomocysteinemia (HHcy) in humans and rodents. To date, scarce information is available about the HHcy effect on insulin secretion, and the l...

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Autores principales: Cruciani-Guglielmacci, Céline, Meneyrol, Kelly, Denom, Jessica, Kassis, Nadim, Rachdi, Latif, Makaci, Fatna, Migrenne-Li, Stéphanie, Daubigney, Fabrice, Georgiadou, Eleni, Denis, Raphaël G., Rodriguez Sanchez-Archidona, Ana, Paul, Jean-Louis, Thorens, Bernard, Rutter, Guy A., Magnan, Christophe, Le Stunff, Hervé, Janel, Nathalie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179272/
https://www.ncbi.nlm.nih.gov/pubmed/35681432
http://dx.doi.org/10.3390/cells11111737
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author Cruciani-Guglielmacci, Céline
Meneyrol, Kelly
Denom, Jessica
Kassis, Nadim
Rachdi, Latif
Makaci, Fatna
Migrenne-Li, Stéphanie
Daubigney, Fabrice
Georgiadou, Eleni
Denis, Raphaël G.
Rodriguez Sanchez-Archidona, Ana
Paul, Jean-Louis
Thorens, Bernard
Rutter, Guy A.
Magnan, Christophe
Le Stunff, Hervé
Janel, Nathalie
author_facet Cruciani-Guglielmacci, Céline
Meneyrol, Kelly
Denom, Jessica
Kassis, Nadim
Rachdi, Latif
Makaci, Fatna
Migrenne-Li, Stéphanie
Daubigney, Fabrice
Georgiadou, Eleni
Denis, Raphaël G.
Rodriguez Sanchez-Archidona, Ana
Paul, Jean-Louis
Thorens, Bernard
Rutter, Guy A.
Magnan, Christophe
Le Stunff, Hervé
Janel, Nathalie
author_sort Cruciani-Guglielmacci, Céline
collection PubMed
description Cystathionine beta synthase (CBS) catalyzes the first step of the transsulfuration pathway from homocysteine to cystathionine, and its deficiency leads to hyperhomocysteinemia (HHcy) in humans and rodents. To date, scarce information is available about the HHcy effect on insulin secretion, and the link between CBS activity and the setting of type 2 diabetes is still unknown. We aimed to decipher the consequences of an inborn defect in CBS on glucose homeostasis in mice. We used a mouse model heterozygous for CBS (CBS+/−) that presented a mild HHcy. Other groups were supplemented with methionine in drinking water to increase the mild to intermediate HHcy, and were submitted to a high-fat diet (HFD). We measured the food intake, body weight gain, body composition, glucose homeostasis, plasma homocysteine level, and CBS activity. We evidenced a defect in the stimulated insulin secretion in CBS+/− mice with mild and intermediate HHcy, while mice with intermediate HHcy under HFD presented an improvement in insulin sensitivity that compensated for the decreased insulin secretion and permitted them to maintain a glucose tolerance similar to the CBS+/+ mice. Islets isolated from CBS+/− mice maintained their ability to respond to the elevated glucose levels, and we showed that a lower parasympathetic tone could, at least in part, be responsible for the insulin secretion defect. Our results emphasize the important role of Hcy metabolic enzymes in insulin secretion and overall glucose homeostasis.
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spelling pubmed-91792722022-06-10 Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse Cruciani-Guglielmacci, Céline Meneyrol, Kelly Denom, Jessica Kassis, Nadim Rachdi, Latif Makaci, Fatna Migrenne-Li, Stéphanie Daubigney, Fabrice Georgiadou, Eleni Denis, Raphaël G. Rodriguez Sanchez-Archidona, Ana Paul, Jean-Louis Thorens, Bernard Rutter, Guy A. Magnan, Christophe Le Stunff, Hervé Janel, Nathalie Cells Article Cystathionine beta synthase (CBS) catalyzes the first step of the transsulfuration pathway from homocysteine to cystathionine, and its deficiency leads to hyperhomocysteinemia (HHcy) in humans and rodents. To date, scarce information is available about the HHcy effect on insulin secretion, and the link between CBS activity and the setting of type 2 diabetes is still unknown. We aimed to decipher the consequences of an inborn defect in CBS on glucose homeostasis in mice. We used a mouse model heterozygous for CBS (CBS+/−) that presented a mild HHcy. Other groups were supplemented with methionine in drinking water to increase the mild to intermediate HHcy, and were submitted to a high-fat diet (HFD). We measured the food intake, body weight gain, body composition, glucose homeostasis, plasma homocysteine level, and CBS activity. We evidenced a defect in the stimulated insulin secretion in CBS+/− mice with mild and intermediate HHcy, while mice with intermediate HHcy under HFD presented an improvement in insulin sensitivity that compensated for the decreased insulin secretion and permitted them to maintain a glucose tolerance similar to the CBS+/+ mice. Islets isolated from CBS+/− mice maintained their ability to respond to the elevated glucose levels, and we showed that a lower parasympathetic tone could, at least in part, be responsible for the insulin secretion defect. Our results emphasize the important role of Hcy metabolic enzymes in insulin secretion and overall glucose homeostasis. MDPI 2022-05-25 /pmc/articles/PMC9179272/ /pubmed/35681432 http://dx.doi.org/10.3390/cells11111737 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cruciani-Guglielmacci, Céline
Meneyrol, Kelly
Denom, Jessica
Kassis, Nadim
Rachdi, Latif
Makaci, Fatna
Migrenne-Li, Stéphanie
Daubigney, Fabrice
Georgiadou, Eleni
Denis, Raphaël G.
Rodriguez Sanchez-Archidona, Ana
Paul, Jean-Louis
Thorens, Bernard
Rutter, Guy A.
Magnan, Christophe
Le Stunff, Hervé
Janel, Nathalie
Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse
title Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse
title_full Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse
title_fullStr Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse
title_full_unstemmed Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse
title_short Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse
title_sort homocysteine metabolism pathway is involved in the control of glucose homeostasis: a cystathionine beta synthase deficiency study in mouse
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179272/
https://www.ncbi.nlm.nih.gov/pubmed/35681432
http://dx.doi.org/10.3390/cells11111737
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