Metformin effect on nontargeted metabolite profiles in patients with type 2 diabetes and in multiple murine tissues. Diabetes 2016;65: 3776-3785

We appreciate the comments of Jegatheesan et al. (1) on our article (2), as well as the remarks of Irving et al. (3). Jegatheesan et al. (1) also summarize citrulline’s beneficial effects, specifically in nonalcoholic fatty liver disease, and characterize this amino acid as a coin with two sides. They suggest citrulline as a marker of insulin resistance as well as an insulin-sensitizing amino acid (1). Although this is an interesting question, it was not the subject of our study and therefore could not be addressed (2). We would like to emphasize that we did not speculate about a direct association between high citrulline and insulin resistance. In fact, …