@article{cruciani-guglielmacci_homocysteine_2022, title = {Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse}, volume = {11}, issn = {2073-4409}, url = {https://www.mdpi.com/2073-4409/11/11/1737}, doi = {10.3390/cells11111737}, shorttitle = {Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis}, 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.}, pages = {1737}, number = {11}, journaltitle = {Cells}, shortjournal = {Cells}, author = {Cruciani-Guglielmacci, Céline and Meneyrol, Kelly and Denom, Jessica and Kassis, Nadim and Rachdi, Latif and Makaci, Fatna and Migrenne-Li, Stéphanie and Daubigney, Fabrice and Georgiadou, Eleni and Denis, Raphaël G. and Rodriguez Sanchez-Archidona, Ana and Paul, Jean-Louis and Thorens, Bernard and Rutter, Guy A. and Magnan, Christophe and Le Stunff, Hervé and Janel, Nathalie}, urldate = {2022-06-22}, date = {2022-05-25}, langid = {english}, }