Described are Neo-Islets comprising: a) dedifferentiated islet cells and mesenchymal and/or adipose stem cells; or b) redifferentiated islet cells and mesenchymal and/or adipose stem cells where the cells have been treated so as to facilitate redifferentiation. Further described herein are methods of generating Neo-Islets, the methods comprising: culturing a) dedifferentiated islet cells and mesenchymal and/or adipose stem cells; or b) redifferentiated islet cells and mesenchymal and/or adipose stem cells; on a surface that promotes the formation of cell clusters. Also described are methods of treating a subject, the methods comprising: providing to the subject Neo-Islets described herein. Additionally described are methods of treating a subject suffering from Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, and other types of insulin-dependent diabetes mellitus, or impaired glucose tolerance by providing to the subject Neo-Islet as described herein. Additionally described are methods of treatment in which intraperitoneal administration of islet-sized Neo-Islets composed of high numbers of mesenchymal stem cells and cultured islet cells, durably and reversibly treats, without hypoglycemia, both streptozotocin-induced and spontaneous Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, and other types of insulin-dependent diabetes mellitus, or impaired glucose tolerance.