Format

Send to

Choose Destination
J Clin Endocrinol Metab. 2016 Mar;101(3):1044-54. doi: 10.1210/jc.2015-2860. Epub 2015 Dec 29.

Evidence of β-Cell Dedifferentiation in Human Type 2 Diabetes.

Author information

1
Departments of Medicine (F.C., R.B., J.Y.K.-M., D.A.) and Surgery (Y.O., P.R.S., L.E.R.), Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Clinical and Experimental Medicine (F.C.), Università Politecnica delle Marche, Ancona, Italy; and Department of Clinical and Experimental Medicine (M.M., L.M., M.S., P.M.), Islet Cell Laboratory, University of Pisa, 56100 Pisa, Italy.

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 (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.

PMID:
26713822
PMCID:
PMC4803182
[Available on 2017-03-01]
DOI:
10.1210/jc.2015-2860
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center