Metabolic syndrome affects over 30% of the global population and is characterised by insulin resistance, obesity and dyslipidaemia, all of which significantly increase the development of chronic metabolic disorders including type 2 diabetes mellitus (T2DM). Over time, existing antihyperglycaemic treatments typically become ineffective due to changes in disease progression, highlighting the importance for the continued development of new therapeutic agents which exert their effects through diverse/ novel mechanisms. This chapter reviews the emerging role of trace amine-associated receptor 1 (TAAR1) as a regulator of metabolic function. Whilst research into TAAR1 agonism has predominantly focused within the central nervous system for application in schizophrenia treatments, emerging preclinical and clinical evidence demonstrates that TAAR1 activation enhances glucose-stimulated insulin secretion and regulates dopaminergic pathways in addiction and reward processes. Comparisons with incretin mimetic therapies, including semaglutide – a glucagon-like peptide-1 (GLP-1) receptor agonist – reveal significant mechanistic overlap, alongside potential advantages including a more favourable metabolic safety profile. Collectively these findings position TAAR1 as a promising target with the potential to address both physiological and neurobehavioural aspects of metabolic disease.

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TAAR1 as a Potential Alternate Molecular Target to GLP-1 for Novel Anti-diabetic, Anti-obesity Medications

  • Rhianna K. Lenham,
  • Fatema Elgammal,
  • Scott V. Harding,
  • Mark D. Berry

摘要

Metabolic syndrome affects over 30% of the global population and is characterised by insulin resistance, obesity and dyslipidaemia, all of which significantly increase the development of chronic metabolic disorders including type 2 diabetes mellitus (T2DM). Over time, existing antihyperglycaemic treatments typically become ineffective due to changes in disease progression, highlighting the importance for the continued development of new therapeutic agents which exert their effects through diverse/ novel mechanisms. This chapter reviews the emerging role of trace amine-associated receptor 1 (TAAR1) as a regulator of metabolic function. Whilst research into TAAR1 agonism has predominantly focused within the central nervous system for application in schizophrenia treatments, emerging preclinical and clinical evidence demonstrates that TAAR1 activation enhances glucose-stimulated insulin secretion and regulates dopaminergic pathways in addiction and reward processes. Comparisons with incretin mimetic therapies, including semaglutide – a glucagon-like peptide-1 (GLP-1) receptor agonist – reveal significant mechanistic overlap, alongside potential advantages including a more favourable metabolic safety profile. Collectively these findings position TAAR1 as a promising target with the potential to address both physiological and neurobehavioural aspects of metabolic disease.