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

BMC Endocrine Disorders

Le Wang¹  Boya Zhang¹  Na Liu¹  Zhongyang Shen¹  Peng Sun¹  Guanqiao Wang¹  Jiaqi Zou¹  Xuejie Ding¹  Rui Liang¹  Yaojuan Liu¹  Tengli Liu²  Shusen Wang³ 

[1] NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, 300384, Tianjin, China;Organ Transplant Center, Tianjin First Central Hospital, Nankai University, Building A, Fukang Road 24#, Nankai area, 300192, Tianjin City, China;NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, 300384, Tianjin, China;Organ Transplant Center, Tianjin First Central Hospital, Nankai University, Building A, Fukang Road 24#, Nankai area, 300192, Tianjin City, China;NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, 300384, Tianjin, China;Tianjin Key Laboratory for Organ Transplantation, Tianjin First Central Hospital, 300192, Tianjin, China;

关键词: NKX6.1;    Age;    Obesity;    HbA1c;    β-Cell dedifferentiation;   

DOI  :  10.1186/s12902-021-00708-7

来源: Springer

【 摘 要 】

BackgroundNKX6.1 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.MethodsWe 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).ResultsOur 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.ConclusionOur 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.

【 授权许可】

CC BY