Expression of Mesenchymal and α-Cell Phenotypic Markers in Islet β-Cells in Recently Diagnosed Diabetes

OBJECTIVE: Relative contributions of reversible β-cell dysfunction and true decrease in β-cell mass in type 2 diabetes remain unclear. Definitive rodent lineage-tracing studies have identified β-cell dedifferentiation and subsequent reprogramming to α-cell fate as a novel mechanism underlying β-cell failure. The aim was to determine whether phenotypes of β-cell dedifferentiation and plasticity are present in human diabetes. RESEARCH DESIGN AND METHODS: Immunofluorescence colocalization studies using classical endocrine and mesenchymal phenotypic markers were undertaken using pancreatic sections and isolated islets from three individuals with diabetes and five nondiabetic control subjects. RESULTS: Intraislet cytoplasmic coexpression of insulin and vimentin, insulin and glucagon, and vimentin and glucagon were demonstrated in all cases. These phenotypes were not present in nondiabetic control subjects. CONCLUSIONS: Coexpression of mesenchymal and α-cell phenotypic markers in human diabetic islet β-cells has been confirmed, providing circumstantial evidence for β-cell dedifferentiation and possible reprogramming to α-cells in clinical diabetes.