PMID- 38432501
OWN - NLM
STAT- MEDLINE
DCOM- 20240408
LR  - 20240514
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 586
DP  - 2024 May 15
TI  - Excess homocysteine inhibits pancreatic beta-cell secretory function by repressing 
      Zbtb20 expression.
PG  - 112195
LID - S0303-7207(24)00051-0 [pii]
LID - 10.1016/j.mce.2024.112195 [doi]
AB  - Homocysteine (Hcy) is a sulfur-containing amino acid. An elevated level of Hcy is 
      a risk factor for diabetes development. However, the mechanism of its effect on 
      pancreatic beta-cell function is unclear. In this study, we constructed a 
      hyperhomocysteinemia (HHcy) mouse model by feeding mice a high methionine diet 
      (HMD). The mice suffered impaired glucose tolerance and reduced insulin 
      secretion. Furthermore, at the cellular level, INS1 cells exhibited impaired 
      insulin secretory function after the Hcy intervention. Transcriptomics revealed 
      that Zbtb20 expression was downregulated and the downstream gene Fbp1 was 
      upregulated in HHcy-induced mice compared with mice fed with normal diet. Insulin 
      secretion could be restored by Zbtb20 overexpression or fructose 
      1,6-bisphosphatase (FBPase) activity inhibition in INS1 cells. In conclusion, our 
      study suggested that Hcy inhibited the insulin secretory function of pancreatic 
      beta-cells by suppressing Zbtb20 expression, leading to the development of diabetes. 
      Zbtb20 may be a key target in the development of diabetes associated with 
      elevated Hcy levels.
CI  - Copyright (c) 2024 Elsevier B.V. All rights reserved.
FAU - Ding, Tianqi
AU  - Ding T
AD  - Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, 
      China.
FAU - Wen, Bo
AU  - Wen B
AD  - Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, 
      China.
FAU - Chen, Jian
AU  - Chen J
AD  - Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, 
      China.
FAU - Chu, Wenbin
AU  - Chu W
AD  - Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, 
      China.
FAU - Fan, Rong
AU  - Fan R
AD  - Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, 
      China; Central Laboratory, Tianjin Xiqing Hospital, Tianjin, 300380, China. 
      Electronic address: prosperity_39@sina.cn.
FAU - Chen, Xuewei
AU  - Chen X
AD  - Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, 
      China. Electronic address: chenxuewei11@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20240301
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Insulin)
RN  - 0 (Zbtb20 protein, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Insulin/metabolism
MH  - Insulin Secretion
MH  - *Glucose Intolerance
MH  - *Diabetes Mellitus
MH  - Transcription Factors/genetics/metabolism
OTO - NOTNLM
OT  - Fbp1
OT  - Hcy
OT  - Insulin resistance
OT  - Pancreatic beta-cell
OT  - Zbtb20
COIS- Declaration of competing interest The authors declare no competing interests.
EDAT- 2024/03/04 00:43
MHDA- 2024/04/08 06:43
CRDT- 2024/03/03 19:17
PHST- 2023/11/27 00:00 [received]
PHST- 2024/02/22 00:00 [revised]
PHST- 2024/02/25 00:00 [accepted]
PHST- 2024/04/08 06:43 [medline]
PHST- 2024/03/04 00:43 [pubmed]
PHST- 2024/03/03 19:17 [entrez]
AID - S0303-7207(24)00051-0 [pii]
AID - 10.1016/j.mce.2024.112195 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2024 May 15;586:112195. doi: 10.1016/j.mce.2024.112195. Epub 
      2024 Mar 1.