Context: Diabetes is associated with a deficit of insulin-producing β-cells. Animal studies show that β-cells become dedifferentiated in diabetes, reverting to a progenitor-like stage, and partly converting to other endocrine cell types. Objective: To determine whether similar processes occur in human type 2 diabetes, we surveyed pancreatic islets from 15 diabetic and 15 nondiabetic organ donors. Design: We scored dedifferentiation using markers of endocrine lineage, β-cell-specific transcription factors, and a newly identified endocrine progenitor cell marker, aldehyde dehydrogenase 1A3. Results: By these criteria, dedifferentiated cells accounted for 31.9% of β-cells in type 2 diabetics vs 8.7% in controls, and for 16.8% vs 6.5% of all endocrine cells (Pβ.001). The number of aldehyde dehydrogenase 1A3-positive/hormone-negative cells was 3-fold higher in diabetics compared with controls. Moreover, β-cell-specific transcription factors were ectopically found in glucagon-and somatostatin-producing cells of diabetic subjects. Conclusions: The data support the view that pancreatic β-cells become dedifferentiated and convert to-and-like cells in human type 2 diabetes. The findings should prompt a reassessment of goals in the prevention and treatment of β-cell dysfunction.

Cinti, F., Bouchi, R., Kim-Muller, J. Y., Ohmura, Y., Sandoval, P. R., Masini, M., Marselli, L., Suleiman, M., Ratner, L. E., Marchetti, P., Accili, D., Evidence of β-cell dedifferentiation in human type 2 diabetes, <<THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM>>, 2016; 101 (3): 1044-1054. [doi:10.1210/jc.2015-2860] [https://hdl.handle.net/10807/231191]

Evidence of β-cell dedifferentiation in human type 2 diabetes

Cinti, Francesca
Primo
;
2016

Abstract

Context: Diabetes is associated with a deficit of insulin-producing β-cells. Animal studies show that β-cells become dedifferentiated in diabetes, reverting to a progenitor-like stage, and partly converting to other endocrine cell types. Objective: To determine whether similar processes occur in human type 2 diabetes, we surveyed pancreatic islets from 15 diabetic and 15 nondiabetic organ donors. Design: We scored dedifferentiation using markers of endocrine lineage, β-cell-specific transcription factors, and a newly identified endocrine progenitor cell marker, aldehyde dehydrogenase 1A3. Results: By these criteria, dedifferentiated cells accounted for 31.9% of β-cells in type 2 diabetics vs 8.7% in controls, and for 16.8% vs 6.5% of all endocrine cells (Pβ.001). The number of aldehyde dehydrogenase 1A3-positive/hormone-negative cells was 3-fold higher in diabetics compared with controls. Moreover, β-cell-specific transcription factors were ectopically found in glucagon-and somatostatin-producing cells of diabetic subjects. Conclusions: The data support the view that pancreatic β-cells become dedifferentiated and convert to-and-like cells in human type 2 diabetes. The findings should prompt a reassessment of goals in the prevention and treatment of β-cell dysfunction.
2016
Inglese
Cinti, F., Bouchi, R., Kim-Muller, J. Y., Ohmura, Y., Sandoval, P. R., Masini, M., Marselli, L., Suleiman, M., Ratner, L. E., Marchetti, P., Accili, D., Evidence of β-cell dedifferentiation in human type 2 diabetes, <<THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM>>, 2016; 101 (3): 1044-1054. [doi:10.1210/jc.2015-2860] [https://hdl.handle.net/10807/231191]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/231191
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