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Published on: June 16, 2011
β-Cell Dedifferentiation in HOMA-βlow and HOMA-βhigh Subjects
Fuyun Kang1,2, Zhuo Zhang3, Hui Fu1,2
1Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Context:
β-Cell dedifferentiation ratio is increased in type 2 diabetes; but its direct link to in vivo β-cell function in human remains unclear.
Objective:
The present study was designed to investigate whether β-cell dedifferentiation in situ was closely associated with β-cell function in vivo and to identify targets crucial for β-cell dedifferentiation/function in human.
Methods:
We acquired homeostasis model assessment of β-cell function (HOMA-β) values, calculated the number of hormone-negative endocrine cells, and evaluated important markers and novel candidates for β-cell dedifferentiation/function on paraneoplastic pancreatic tissues from 13 patients with benign pancreatic cystic neoplasm or intrapancreatic accessory spleen.
Results:
Both the β-cell dedifferentiation ratio and the dedifferentiation marker (Aldh1a3) were inversely related to in vivo β-cell function (HOMA-β) and in situ β-cell functional markers Glut2 and Ucn3 in humans. Moreover, the islets from HOMA-βlow subjects were manifested as (1) increased β-cell dedifferentiation ratio, (2) enriched dedifferentiation maker Aldh1a3, and (3) lower expression of Glut2 and Ucn3 compared with those from HOMA-βhigh subjects. We found that basic leucine zipper transcription factor 2 (Bach2) expression was significantly induced in islets from HOMA-βlow patients and was positively correlated with the ratio of β-cell dedifferentiation in humans.
Conclusion:
Our findings emphasize the contribution of β-cell dedifferentiation to β-cell dysfunction in humans. Bach2 induction in β-cells with higher frequency of dedifferentiation observed in HOMA-βlow subjects reinforces its distinctive role as a pharmaceutical target of β-cell dedifferentiation for the treatment of people with diabetes.
