Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity

Jessica T. Y. Yue, Mona A. Abraham, Paige V. Bauer, Mary P. LaPierre, Peili Wang, Frank A. Duca, Beatrice M. Filippi, Owen Chan and Tony K. T. Lam ()
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Jessica T. Y. Yue: UHN
Mona A. Abraham: UHN
Paige V. Bauer: UHN
Mary P. LaPierre: UHN
Peili Wang: Section of Endocrinology, Yale University School of Medicine
Frank A. Duca: UHN
Beatrice M. Filippi: UHN
Owen Chan: Section of Endocrinology, Yale University School of Medicine
Tony K. T. Lam: UHN

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Impaired glucose homeostasis and energy balance are integral to the pathophysiology of diabetes and obesity. Here we show that administration of a glycine transporter 1 (GlyT1) inhibitor, or molecular GlyT1 knockdown, in the dorsal vagal complex (DVC) suppresses glucose production, increases glucose tolerance and reduces food intake and body weight gain in healthy, obese and diabetic rats. These findings provide proof of concept that GlyT1 inhibition in the brain improves glucose and energy homeostasis. Considering the clinical safety and efficacy of GlyT1 inhibitors in raising glycine levels in clinical trials for schizophrenia, we propose that GlyT1 inhibitors have the potential to be repurposed as a treatment of both obesity and diabetes.

Date: 2016
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DOI: 10.1038/ncomms13501

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