PMID- 36040726
OWN - NLM
STAT- MEDLINE
DCOM- 20221118
LR  - 20221118
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 46
IP  - 12
DP  - 2022 Dec
TI  - Overexpression of TRIM32 promotes pancreatic beta-cell autophagic cell death through 
      Akt/mTOR pathway under high glucose conditions.
PG  - 2095-2106
LID - 10.1002/cbin.11897 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is a growing worldwide epidemic and is 
      characterized by progressive pancreatic beta-cell dysfunction and insulin 
      resistance. Tripartite motif protein 32 (TRIM32) belongs to the TRIM family 
      protein and has been shown to be involve in insulin resistance in skeletal muscle 
      and the liver. However, the effect of TRIM32 on pancreatic beta-cell dysfunction and 
      its mechanism remains unknown. In the current study, we found that serum TRIM32 
      concentrations of T2DM in patients were significantly elevated compared to those 
      in healthy controls, which indicated that TRIM32 might be used as a diagnostic 
      biomarker in T2DM patients. In INS-1 cells, exposure to high glucose (HG) 
      conditions caused a significant elevation in TRIM32 expression and TRIM32 was 
      located in the nucleus. Overexpression of TRIM32 in INS-1 cells exacerbated the 
      effects of HG-induced autophagy and impaired insulin secretion. In contrast, the 
      silencing of TRIM32 produced the opposite effect. Furthermore, TRIM32 
      overexpression decreased the phosphorylation levels of Akt and mTOR under HG 
      conditions. However, the activation of Akt/mTOR by MHY1485 reversed the effects 
      of TRIM32 on HG-treated INS-1 cells. Collectively, the present results suggested 
      that TRIM32 participates in the development of T2DM by modulating autophagic cell 
      death and insulin secretion, which might occur through the Akt/mTOR pathway. 
      Thus, TRIM32 might be a promising target in T2DM therapy.
CI  - (c) 2022 International Federation for Cell Biology.
FAU - Wan, Tingting
AU  - Wan T
AD  - Department of Endocrinology, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
AD  - The Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, 
      Heilongjiang, China.
FAU - Wang, Yidan
AU  - Wang Y
AD  - Department of Endocrinology, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
AD  - The Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, 
      Heilongjiang, China.
FAU - Wang, Chunxu
AU  - Wang C
AD  - The Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, 
      Heilongjiang, China.
AD  - Department of Hematology, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
FAU - Wang, Hongjie
AU  - Wang H
AD  - Department of Endocrinology, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
FAU - Li, Xiudan
AU  - Li X
AD  - Department of Endocrinology, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
AD  - The Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, 
      Heilongjiang, China.
FAU - Li, Yanbo
AU  - Li Y
AUID- ORCID: 0000-0002-2562-7956
AD  - Department of Endocrinology, The First Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, China.
LA  - eng
GR  - 2022A1515012626/Natural Science Foundation of Guangdong Province/
GR  - 81770820/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20220830
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (Tripartite Motif Proteins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.3.2.27 (TRIM32 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Humans
MH  - Tripartite Motif Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - *Autophagic Cell Death
MH  - *Insulin Resistance
MH  - *Diabetes Mellitus, Type 2
MH  - Ubiquitin-Protein Ligases/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Glucose/pharmacology/metabolism
MH  - Transcription Factors/metabolism
OTO - NOTNLM
OT  - Akt/mTOR
OT  - INS-1 cells
OT  - TRIM32
OT  - autophagic cell death
OT  - insulin secretion
OT  - type 2 diabetes mellitus
EDAT- 2022/08/31 06:00
MHDA- 2022/11/19 06:00
CRDT- 2022/08/30 11:32
PHST- 2022/07/25 00:00 [revised]
PHST- 2021/12/16 00:00 [received]
PHST- 2022/08/10 00:00 [accepted]
PHST- 2022/08/31 06:00 [pubmed]
PHST- 2022/11/19 06:00 [medline]
PHST- 2022/08/30 11:32 [entrez]
AID - 10.1002/cbin.11897 [doi]
PST - ppublish
SO  - Cell Biol Int. 2022 Dec;46(12):2095-2106. doi: 10.1002/cbin.11897. Epub 2022 Aug 
      30.