Beta cells arise from glucose transporter type 2 (Glut2)-expressing epithelial cells of the developing rat pancreas.

We observe Glut2 protein in day 11 (E11) rat embryos in an endodermal domain containing the pancreatic primordium. Glut2 expression continues as the endodermal epithelium evaginates into the surrounding mesenchyme to form the pancreatic buds. Cells of the dorsal and ventral pancreatic buds maintain Glut2 expression as the epithelium grows and branches to form ducts. As acini form at the ends of the ducts, acinar cells cease Glut2 expression. Insulin protein is first detected in small clusters at the interface between pancreatic epithelium and mesenchyme. These clusters disperse into the interstitial tissue between E13 and E17. At E17 a distinct, larger population of insulin-expressing cells arises in the Glut2-expressing ductal network. Insulin- and Glut2-coexpressing cells then appear to segregate into large aggregates to form the beta cells of the islets of Langerhans. These observations support the hypothesis that two biologically distinct populations of insulin-expressing cells arise during pancreas formation.