Impaired “Glycine”-mia in Type 2 Diabetes and Potential Mechanisms Contributing to Glucose Homeostasis

: The onset and/or progression of type 2 diabetes (T2D) can be prevented if intervention is early enough. As such, much effort has been placed on the search for indicators predictive of prediabetes and disease onset or progression. An increasing body of evidence suggests that changes in plasma glycine may be one such biomarker. Circulating glycine levels are consistently low in patients with T2D. Levels of this nonessential amino acid correlate negatively with obesity and insulin resistance. Plasma glycine correlates positively with glucose disposal, and rises with interventions such as exercise and bariatric surgery that improve glucose homeostasis. A role for glycine in the regulation of glucose, beyond being a potential biomarker, is less clear, however. Dietary glycine supplementation increases insulin, reduces systemic inflammation, and improves glucose tolerance. Emerging evidence suggests that glycine, a neurotransmitter, also acts directly on target tissues that include the endocrine pancreas and the brain via glycine receptors and as a coligand for N-methyl-d-aspartate glutamate receptors to control insulin secretion and liver glucose output, respectively. Here, we review the current evidence supporting a role for glycine in glucose homeostasis via its central and peripheral actions and changes that occur in T2D.