Sweet killers: Animal toxins that mimic glucoregulatory hormones

Glucose homeostasis is regulated by a complex interplay of endocrine signals, primarily involving insulin, glucagon, and incretin hormones, such as glucagon-like peptide-1 (GLP-1). Disruption of this balance underlies metabolic disorders like type 2 diabetes, a condition of growing global concern. In recent years, animal-derived toxins have emerged as a novel and underexplored source of bioactive compounds capable of modulating key pathways involved in glucose regulation. This review provides an overview of the endocrine control of glucose metabolism, followed by an in-depth examination of animal toxins that mimic or modulate the activity of insulin and GLP-1, as well as those that interfere with glucagon signaling, focusing on their pharmacological relevance. These naturally evolved molecules offer unique mechanisms of action and high target specificity, making them valuable leads for drug development. Several venom-derived compounds have already shown promise in preclinical and clinical studies, reinforcing their potential as templates for next-generation antidiabetic therapies. We also discuss the translational implications of these discoveries, highlight current challenges in their therapeutic development, and propose future directions for researches which crosstalk between Toxinology and Endocrinology.