Work

β-Cell Dedifferentiation in HOMA-βlow and HOMA-βhigh Subjects

Year: 2024

Type: article

Abstract: 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.

Source: The Journal of Clinical Endocrinology & Metabolism

DOI: 10.1210/clinem/dgae538

Authors: Fuyun Kang, Zhuo Zhang, Hui Fu, Jiajun Sun, Jun Zhang, Qidi Wang

Institutions: Shanghai Jiao Tong University, Ruijin Hospital

Language: English

Topic: Pancreatic function and diabetes

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,938