Increased frequency of β cells with abnormal NKX6.1 expression in type 2 diabetes but not in subjects with higher risk for type 2 diabetes
| Autor: | Jiaqi Zou, Peng Sun, Le Wang, Tengli Liu, Shusen Wang, Guanqiao Wang, Xuejie Ding, Zhongyang Shen, Yaojuan Liu, Boya Zhang, Rui Liang, Na Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine endocrine system diseases Endocrinology Diabetes and Metabolism medicine.medical_treatment Cell Cell Count Chromosomal translocation Type 2 diabetes lcsh:Diseases of the endocrine glands. Clinical endocrinology chemistry.chemical_compound 0302 clinical medicine Risk Factors Insulin-Secreting Cells Medicine Cell Differentiation General Medicine Middle Aged medicine.anatomical_structure embryonic structures Female Autopsy Research Article Adult medicine.medical_specialty animal structures HbA1c 030209 endocrinology & metabolism Prediabetic State 03 medical and health sciences Age Diabetes mellitus Internal medicine Humans Obesity NKX6.1 Aged Glycated Hemoglobin Homeodomain Proteins β-Cell dedifferentiation lcsh:RC648-665 business.industry Insulin Type 2 Diabetes Mellitus nutritional and metabolic diseases medicine.disease 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 chemistry Cytoplasm Case-Control Studies Glycated hemoglobin business |
| Zdroj: | BMC Endocrine Disorders, Vol 21, Iss 1, Pp 1-7 (2021) BMC Endocrine Disorders |
| ISSN: | 1472-6823 |
| Popis: | Background NKX6.1 is a transcription factor for insulin, as well as a marker for β cell maturity. Abnormal NKX6.1 expression in β cells, such as translocation from the nucleus to cytoplasm or lost expression, has been shown as a marker for β cell dedifferentiation. Methods We obtained pancreatic sections from organ donors and immunofluorescence staining with NKX6.1 and insulin was performed to characterize NKX6.1 expression in subjects with or without type 2 diabetes mellitus (T2DM). Results Our results showed that cells with insulin expression but no nucleic NKX6.1 expression (NKX6.1Nuc-Ins+), and cells with cytoplasmic NKX6.1 expression but no insulin expression (NKX6.1cytIns−) were significantly increased in T2DM subjects and positively correlated with glycated hemoglobin (HbA1c), indicating the elevated β cell dedifferentiation with NKX6.1 inactivation in T2DM. To investigate whether β cell dedifferentiation has initiated in subjects with higher risks for T2DM, we next analyzed the association between β-cell dedifferentiation level in ND subjects with different ages, body mass index, and HbA1c. The results showed the absolute number and percentage of dedifferentiated β cells with NKX6.1 inactivation did not significantly change in subjects with advanced aging, obesity, or modest hyperglycemia, indicating that the β cell dedifferentiation might mainly occur after T2DM was diagnosed. Conclusion Our results suggested that NKX6.1 expression in β cells was changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1Nuc-Ins+ and NKX6.1cytIns− cells. This abnormality did not occur more frequently in subjects with a higher risk for T2DM, suggesting that β cell dedifferentiation might be secondary to the pathological changes in T2DM. |
| Databáze: | OpenAIRE |
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