PMID- 27052187
OWN - NLM
STAT- MEDLINE
DCOM- 20170216
LR  - 20171116
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 13
IP  - 5
DP  - 2016 May
TI  - 3-Deoxyglucosone induces insulin resistance by impairing insulin signaling in 
      HepG2 cells.
PG  - 4506-12
LID - 10.3892/mmr.2016.5081 [doi]
AB  - 3-Deoxyglucosone (3DG), a highly reactive dicarbonyl intermediate generated 
      during glycation, has been confirmed to be markedly elevated in the plasma of 
      patients with diabetes. Our previous study found that there is an association 
      between increasing accumulation of plasma 3DG and impaired glucose regulation in 
      non-diabetic seniors (females, >50 years old; males, >55 years old). It was also 
      found that 3DG led to impaired plasma glucose homeostasis in healthy mice, 
      however, the mechanisms underlying the deleterious effect of 3DG in diabetes 
      remain to be fully elucidated. The present study aimed to investigate the ability 
      of 3DG to cause hepatic insulin resistance in a cell model by assessing glucose 
      uptake and glycogen content. In addition, the molecular signaling events, 
      including the phosphoinositide 3‑kinase (PI3K)/AKT/glucose transporter 2 (GLUT2) 
      and PI3K/AKT/glycogen synthase kinase‑3 (GSK‑3) pathways, which affect hepatic 
      insulin resistance, were further investigated using Western blot analysis. The 
      results showed that 3DG (10‑300 ng/ml) had no significant effect on HepG2 cell 
      viability, however, the viability of the HepG2 cells decreased with exposure to 
      concentrations of 500 and 1,000 ng/ml. Treatment with non‑cytotoxic 3DG 
      concentrations resulted in decreased uptake of glucose and glycogen content with 
      insulin stimulation, but not under basal conditions. The insulin‑induced 
      expression of GLUT2 and p‑GSK‑3 were eliminated by 3DG (80 and 300 ng/ml), in 
      addition to inhibiting the phosphorylation of downstream effectors of the insulin 
      signaling pathway, including insulin receptor substrate 1, PI3K and AKT. In 
      conclusion, the findings of the present study indicated that the addition of 
      exogenous 3DG directly contributed to the induction of insulin resistance by 
      impairing insulin signaling in the HepG2 cells, which suggested that 3DG may be 
      involved in worsening of the diabetic condition.
FAU - Liang, Guoqiang
AU  - Liang G
AD  - Basic Research Laboratory, Suzhou Academy of Wumen Chinese Medicine, Suzhou 
      Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215003, P.R. China.
FAU - Wang, Fei
AU  - Wang F
AD  - Basic Research Laboratory, Suzhou Academy of Wumen Chinese Medicine, Suzhou 
      Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215003, P.R. China.
FAU - Song, Xiudao
AU  - Song X
AD  - Basic Research Laboratory, Suzhou Academy of Wumen Chinese Medicine, Suzhou 
      Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215003, P.R. China.
FAU - Zhang, Lurong
AU  - Zhang L
AD  - Basic Research Laboratory, Suzhou Academy of Wumen Chinese Medicine, Suzhou 
      Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215003, P.R. China.
FAU - Qian, Zhen
AU  - Qian Z
AD  - Basic Research Laboratory, Suzhou Academy of Wumen Chinese Medicine, Suzhou 
      Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215003, P.R. China.
FAU - Jiang, Guorong
AU  - Jiang G
AD  - Basic Research Laboratory, Suzhou Academy of Wumen Chinese Medicine, Suzhou 
      Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215003, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20160404
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Insulin)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EXV5374VEY (3-deoxyglucosone)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Deoxyglucose/*analogs & derivatives/pharmacology
MH  - Female
MH  - Hep G2 Cells
MH  - Humans
MH  - Insulin/*metabolism
MH  - *Insulin Resistance
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Signal Transduction/*drug effects
EDAT- 2016/04/08 06:00
MHDA- 2017/02/17 06:00
CRDT- 2016/04/08 06:00
PHST- 2015/04/25 00:00 [received]
PHST- 2016/03/01 00:00 [accepted]
PHST- 2016/04/08 06:00 [entrez]
PHST- 2016/04/08 06:00 [pubmed]
PHST- 2017/02/17 06:00 [medline]
AID - 10.3892/mmr.2016.5081 [doi]
PST - ppublish
SO  - Mol Med Rep. 2016 May;13(5):4506-12. doi: 10.3892/mmr.2016.5081. Epub 2016 Apr 4.