JunD, a member of the AP-1 (activator protein-1) family of transcription factors, can activate or repress diverse target genes. Precise control of its expression and protein-protein interactions modulate processes like tumor angiogenesis, cellular differentiation, proliferation, and apoptosis [4]. JunD is involved in multiple pathways and is of great biological importance, with its inappropriate activity contributing to neoplastic, metabolic, and viral diseases. Genetic models are valuable for studying its functions.

In pancreatic β-cells, JunD has been shown to regulate function by altering lipid accumulation. Palmitic acid stimulation induces JunD overexpression, impairs glucose-stimulated insulin secretion, and increases intracellular lipid accumulation. Gene silencing of JunD reverses these lipotoxic effects [1]. In the heart, hyperglycemia-induced reactive oxygen species lead to reduced JunD mRNA and protein expression in the myocardium of diabetic mice, associated with oxidative stress and left ventricular dysfunction. Cardiac-specific overexpression of JunD protects against hyperglycemia-induced cardiac dysfunction [2]. In pancreatic β-cells under metabolic stress, JUND upregulation was found in mouse islets cultured with high glucose and free fatty acid, and its depletion reduced oxidative stress and apoptosis [3].

In conclusion, JunD plays essential roles in pancreatic β-cell function, myocardial function under hyperglycemic conditions, and pancreatic β-cell survival during metabolic stress. Mouse models, including those with gene silencing or overexpression, have been crucial in revealing these functions, providing insights into potential therapeutic strategies for diabetes-related pancreatic and cardiac dysfunctions.