Imidazole propionate is a metabolite of histidine. It is formed from histidine via a urocanate intermediate in gut microbiota by urocanate reductase (urdA). Imidazole propionate (100 µM) decreases protein levels of insulin receptor substrate 1 (IRS-1), IRS-2, and phosphorylated Akt and increases levels of the mTORC1 activation marker phosphorylated p70 ribosomal S6 kinase (p70S6K) in primary mouse hepatocytes. It induces deficits in glucose tolerance in germ-free and conventionally raised mice when administered at doses of 500 and 100 µg/animal, respectively. It also prevents reductions in blood glucose levels induced by metformin in mice. Plasma levels of imidazole propionate are increased in patients with type 2 diabetes.