INS and diabetes mellitus: Mice that lacked peripheral tryptophan hydroxylase (Tph1 2/2), which is essential for serotonin synthesis (Tph 1 −/−), developed diabetes and showed impaired insulin secretion, abnormalities that were restored to normal by administration of 5-hydroxytryptophan, the precursor of serotonin, that increased intracellular serotonin, bypassing the rate-limiting step (335, 337).