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

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

J Clin Endocrinol Metab. 2015 Dec 29;:jc20152860

Authors: Cinti F, Bouchi R, Kim-Muller JY, Ohmura Y, Rodrigo Sandoval P, Masini M, Marselli L, Suleiman M, Ratner LE, Marchetti P, Accili D

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 non-diabetic 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 (ALDH1A3).
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<0.001). The number of ALDH1A3-positive/hormone-negative cells was threefold higher in diabetics compared to 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 [PubMed - as supplied by publisher]

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