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

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 11; p. 1737
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-05-2022; MDPI
• Subjects: Amino acid metabolism; Analysis; Animals; autonomic nervous system; Body composition; Body weight gain; Cardiovascular diseases; Care and treatment; Cystathionine b-synthase; Cystathionine beta-Synthase - metabolism; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Diagnosis; Diet; Drinking water; Enzymes; Food; Food intake; Glucose; Glucose metabolism; Glucose tolerance; Health aspects; High fat diet; Homeostasis; Homocysteine; Homocystinuria - metabolism; Hyperhomocysteinemia; Hyperhomocysteinemia - metabolism; Insulin; Insulin resistance; Insulin secretion; Life Sciences; Liver diseases; Metabolism; Methionine; Mice; Pancreas; Parasympathetic nervous system; Plasma; Prevention; Risk factors; Secretion; Thrombosis; type 2 diabetes; France; United States > US; hyperhomocysteinemia; autonomic nervous system; type 2 diabetes; insulin secretion; Animals, Glucose, Diabetes Mellitus, Type 2, insulin secretion, Mice, Homeostasis, autonomic nervous system, Cystathionine beta-Synthase, Homocysteine, Homocystinuria, hyperhomocysteinemia, Hyperhomocysteinemia, type 2 diabetes
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11111737

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.