Impressive work. Could there be alternative explanations for your findings? In clinical practice, phenylbutyrate is used for patients with urea cycle defects and scavenges glutamine. It there anything known about the relationship between glutamine and insulin resistante/T2D?
Thank you for your interesting question!
Indeed, phenylbutyrate activates the glutamine synthetase and binds with glutamine, which will be removed in urine. So it is expected that glutamate/glutamine levels will be lower. However, we did not found significant differences in glutamate/glutamine levels after the treatment with NaPB in the participants. It could be hypothesized that lower levels of glutamine will result in lower gluconeogenesis. Also in the literature there is evidence that the gluconeogenic amino acids, glutamate and glutamine, are associated with risk of T2DM.