Evidence of β-cell dedifferentiation in human type 2 diabetes
F Cinti, R Bouchi, JY Kim-Muller… - The Journal of …, 2016 - academic.oup.com
F Cinti, R Bouchi, JY Kim-Muller, Y Ohmura, PR Sandoval, M Masini, L Marselli, M Suleiman…
The Journal of Clinical Endocrinology & Metabolism, 2016•academic.oup.comContext: 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 …
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 …
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 (P < .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 α- and δ-“like” cells in human type 2 diabetes. The findings should prompt a reassessment of goals in the prevention and treatment of β-cell dysfunction.
Oxford University Press