Commentary: 3-Iodothyronamine Reduces Insulin Secretion In Vitro via a Mitochondrial Mechanism

Lehmphul et al. report the effect of 3-iodothyronamine in reducing insulin release in a model of immortalized pancreatic β-cells. Notwithstanding the simplified β-cell model used, this article offers an opportunity to reconsider, possibly under a new light, an old issue of research, which excited people working on amine oxidases (AOs) in the last 20 years. Toward this aim, we would like to propose some points of reflection to the scientific community working on 3-iodothyronamine and thyroid hormone metabolites: 1. the paper indicates that 3-iodothyronamine reduces insulin release with a mechanism mediated, at least in part, by its oxidative metabolite, the 3-iodothyroacetic acid, produced by mitochondrial monoamine oxidase (MAOs), type B (MAO-B) activity. This finding, confirming our observations and hypothesis on the role of 3-iodothyronamine as a source of active metabolites (1, 2), demonstrates for the first time that 3-iodothyronamine is a substrate for MAO-B, the MAO isoform in search of substrates and of functions; 2. the degradation of 3-iodothyronamine by MAO-B, with production of the corresponding aldehyde and hydrogen peroxide (H2O2), potentially represents a self-standing mechanism independently of 3-iodothyronamine receptor activation on pancreatic cells. Amine oxidases are a heterogeneous class of enzymes, including MAOs (type A and B) and semicarbazide-sensitive amine oxidases (SSAOs). While MAOs are ubiquitous enzymes, being linked to the outer mitochondrial membrane (active site facing the cytoplasm), plasma membrane SSAOs can have selective and species-specific tissue/cell expression. In addition, MAOs and SSAOs are distinguishable by inhibitor sensitivity, substrate selectivity and affinity, and subcellular localization. Noradrenaline and serotonin are among MAO-A substrates, dopamine and other trace amines, including tyramine and β-phenylethylamine, are MAO-A, B, and SSAO substrates. Up to now, direct evidence that 3-iodothyronamine is a substrate for MAO-A is lacking. However, now we know that 3-iodothyroanime is a substrate for MAO-B.