Homocysteine metabolism pathway is involved in the control of glucose homeostasis: a cystathionine beta synthase deficiency study in mouse
File(s)cells-11-01737-v2.pdf (7.76 MB)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2022-05-25
Online Publication Date
2022-06-21T08:33:40Z
Date Acceptance
2022-05-20
ISSN
2073-4409
Publisher
MDPI
Journal / Book Title
Cells
Volume
11
Issue
11
Copyright Statement
© 2022 by the authors.
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/).
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/).
Sponsor
MRC Programme Grant
Wellcome Trust
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35681432
cells11111737
Grant Number
MR/R022259/1
212625/Z/18/Z
Subjects
autonomic nervous system
hyperhomocysteinemia
insulin secretion
type 2 diabetes
Animals
Cystathionine beta-Synthase
Diabetes Mellitus, Type 2
Glucose
Homeostasis
Homocysteine
Homocystinuria
Hyperhomocysteinemia
Mice
Animals
Mice
Homocystinuria
Hyperhomocysteinemia
Diabetes Mellitus, Type 2
Cystathionine beta-Synthase
Glucose
Homocysteine
Homeostasis
autonomic nervous system
hyperhomocysteinemia
insulin secretion
type 2 diabetes
Animals
Cystathionine beta-Synthase
Diabetes Mellitus, Type 2
Glucose
Homeostasis
Homocysteine
Homocystinuria
Hyperhomocysteinemia
Mice
Publication Status
Published
Country
Switzerland
Article Number
ARTN 1737