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To facilitate studies in human salivary gland disease, we developed a rapid protocol for 3D hiPSC-derived salivary gland organoids that recapitulate human fetal salivary gland gene expression and function, have both ductal and acinar cell types, secretory capacity, and the ability to respond to cholinergic agonism. Oral health issues resulting from diabetes mellitus have been attributed to salivary gland dysfunction, leading to chronic xerostomia and increased dental caries. To study diabetic salivary gland hypofunction, we further developed a diabetic model, demonstrating diabetic hallmarks including FOXO1 nuclear localization, AGE-RAGE signaling, and defective oxidative phosphorylation, which were by treatment with the diabetic drug Metformin. 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