PMID- 34703256
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220427
IS  - 1178-7007 (Print)
IS  - 1178-7007 (Electronic)
IS  - 1178-7007 (Linking)
VI  - 14
DP  - 2021
TI  - ANGPTL8/Betatrophin Improves Glucose Tolerance in Older Mice and Metabolomic 
      Analysis Reveals Its Role in Insulin Resistance in HepG2 Cells.
PG  - 4209-4221
LID - 10.2147/DMSO.S330700 [doi]
AB  - BACKGROUND: Insulin resistance is a determining factor in the pathophysiology of 
      type 2 diabetes mellitus (T2DM). Angiopoietin-like protein 8 (ANGPTL8, also known 
      as betatrophin), associated with glucose homeostasis and lipid metabolism, has 
      attracted attention. But its mechanism in glucose metabolism remains unclear. 
      This study aimed to explore the effect of ANGPTL8/betatrophin on glucose 
      tolerance in Kunming (KM) mice of different ages and metabolic profiles in 
      insulin-resistant HepG2 cells. Our study may provide a new perspective of 
      ANGPTL8/betatrophin in insulin resistance from the metabolic changes. METHODS: 
      Oral glucose tolerance test was performed in KM mice of different ages. Insulin 
      concentration was measured by using a quantitative enzyme-linked immunosorbent 
      assay (ELISA). ANGPTL8/betatrophin knockouts in HepG2 cells were established with 
      clustered regularly interspaced short palindromic repeats 
      (CRISPR)/CRISPR-associated (Cas) protein 9 (CRISPR/Cas9) system. Cell counting 
      kit-8 (CCK-8) assay was used to determine cell viability after gene knockout. The 
      effect of ANGPTL8/betatrophin on the metabolomic changes was evaluated in high 
      insulin-induced insulin-resistant HepG2 cells by an ultra-performance liquid 
      chromatography-tandem mass spectrometry (UPLC-MS/MS) method. RESULTS: 
      ANGPTL8/betatrophin improved glucose tolerance in older mice not by altering the 
      concentration of insulin. Cell growth was affected in ANGPTL8/betatrophin 
      knockout HepG2. Based on UPLC-MS/MS, compared with wild type insulin-resistant 
      HepG2 cells, we identified 83 differential metabolites in ANGPTL8/betatrophin 
      knockout HepG2 cells after high insulin induction. Among the 14 differential 
      up-regulated metabolites, D-mannose had the highest fold change. In 
      insulin-resistant HepG2 cells, ANGPTL8/betatrophin knockout exerted an effect on 
      the amino acid metabolism, carbohydrate metabolism, metabolism of cofactors and 
      vitamins, lipid metabolism, nucleotide metabolism, and genetic information 
      processing pathway. CONCLUSION: This study identified the effect of 
      ANGPTL8/betatrophin on glucose tolerance in mice of different ages and metabolic 
      profiles in insulin-resistant HepG2 cells. These findings may contribute to a new 
      understanding of its role in glucose metabolism in the context of insulin 
      resistance.
CI  - (c) 2021 Xu et al.
FAU - Xu, Fangfang
AU  - Xu F
AUID- ORCID: 0000-0003-1364-7930
AD  - Clinical Medical Research Center, Department of Research and Discipline 
      Development, Henan Provincial People's Hospital, Zhengzhou University People's 
      Hospital, Henan University People's Hospital, School of Clinical Medicine, Henan 
      University, Zhengzhou, Henan, 450003, People's Republic of China.
FAU - Wang, Nan
AU  - Wang N
AD  - Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, 
      Beijing, 100081, People's Republic of China.
FAU - Li, Gangqiang
AU  - Li G
AD  - Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, 
      Beijing, 100081, People's Republic of China.
FAU - Tian, Dandan
AU  - Tian D
AD  - Department of Hypertension, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Zhengzhou, Henan, 450003, People's Republic of 
      China.
FAU - Shi, Xiaoyang
AU  - Shi X
AD  - Department of Endocrinology, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Zhengzhou, Henan, 450003, People's Republic of 
      China.
LA  - eng
PT  - Journal Article
DEP - 20211011
PL  - New Zealand
TA  - Diabetes Metab Syndr Obes
JT  - Diabetes, metabolic syndrome and obesity : targets and therapy
JID - 101515585
PMC - PMC8523517
OTO - NOTNLM
OT  - ANGPTL8/betatrophin
OT  - CRISPR/Cas9 technology
OT  - glucose tolerance
OT  - inflammation
OT  - insulin resistance
OT  - metabolomics
COIS- The authors declare that they have no competing interests.
EDAT- 2021/10/28 06:00
MHDA- 2021/10/28 06:01
PMCR- 2021/10/11
CRDT- 2021/10/27 07:04
PHST- 2021/07/22 00:00 [received]
PHST- 2021/09/23 00:00 [accepted]
PHST- 2021/10/27 07:04 [entrez]
PHST- 2021/10/28 06:00 [pubmed]
PHST- 2021/10/28 06:01 [medline]
PHST- 2021/10/11 00:00 [pmc-release]
AID - 330700 [pii]
AID - 10.2147/DMSO.S330700 [doi]
PST - epublish
SO  - Diabetes Metab Syndr Obes. 2021 Oct 11;14:4209-4221. doi: 10.2147/DMSO.S330700. 
      eCollection 2021.