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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9179272 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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