PMID- 32510127
OWN - NLM
STAT- MEDLINE
DCOM- 20201231
LR  - 20201231
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 477
IP  - 12
DP  - 2020 Jun 26
TI  - DhHP-6 ameliorates hepatic oxidative stress and insulin resistance in type 2 
      diabetes mellitus through the PI3K/AKT and AMPK pathway.
PG  - 2363-2381
LID - 10.1042/BCJ20200402 [doi]
AB  - Insulin resistance is one major features of type 2 diabetes mellitus (T2DM). 
      Deuterohemin-betaAla-His-Thr-Val-Glu-Lys (DhHP-6), a novel microperoxidase mimetic 
      designed and synthesized based on microperoxidase 11 (MP-11), can scavenge 
      reactive oxygen species (ROS) in vivo. In our previous studies, we showed that 
      oral DhHP-6 could reduce blood glucose and improve insulin resistance. To 
      investigate the mechanisms of how DhHP-6 ameliorates oxidative stress and insulin 
      resistance, we established T2DM mouse models and glucosamine-induced HepG2 cell 
      insulin resistance models. The results suggested that DhHP-6 decreased blood 
      glucose, increased antioxidant enzyme activity, and inhibited glycogen synthesis 
      in T2DM mice. In addition, DhHP-6 improved insulin resistance by activating 
      phosphatidylinositol 3-kinase (PI3K)/AKT, and AMP-activated protein kinase (AMPK) 
      pathway in T2DM mice. Furthermore, DhHP-6 also activated PI3K/AKT and AMPK 
      pathway in glucosamine-induced HepG2 cells. However, LY294002 did not completely 
      inhibit AKT phosphorylation, and partially inhibited AMPK phosphorylation, whilst 
      compound C only partially reduced AMPK phosphorylation, and also partially 
      inhibited AKT phosphorylation, suggesting that AKT and AMPK interact to improve 
      insulin resistance. Thus, these data suggest that DhHP-6 attenuates insulin 
      resistance via the PI3K/AKT and AMPK pathway.
CI  - (c) 2020 The Author(s). Published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Wang, Kai
AU  - Wang K
AD  - School of Life Sciences, Jilin University, Changchun 130012, China.
FAU - Liang, Yuting
AU  - Liang Y
AD  - School of Life Sciences, Jilin University, Changchun 130012, China.
FAU - Su, Yu
AU  - Su Y
AD  - School of Life Sciences, Jilin University, Changchun 130012, China.
FAU - Wang, Liping
AU  - Wang L
AD  - School of Life Sciences, Jilin University, Changchun 130012, China.
AD  - Key Laboratory for Molecular Enzymology and Engineering, the Ministry of 
      Education, Jilin University, Changchun 130012, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Oligopeptides)
RN  - 0 (deuterohemin-alanyl-histidyl-threonyl-valyl-glutamyl-lysine)
RN  - 743LRP9S7N (Hemin)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*metabolism
MH  - Animals
MH  - Diabetes Mellitus, Experimental/*drug therapy/etiology/metabolism/pathology
MH  - Diabetes Mellitus, Type 2/*drug therapy/etiology/metabolism/pathology
MH  - Diet, High-Fat/adverse effects
MH  - Glucose/metabolism
MH  - Hemin/*analogs & derivatives/pharmacology
MH  - Hep G2 Cells
MH  - Humans
MH  - Hypoglycemic Agents
MH  - Insulin Resistance
MH  - Lipid Metabolism
MH  - Liver/drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oligopeptides/*pharmacology
MH  - Oxidative Stress/*drug effects
MH  - Phosphatidylinositol 3-Kinase/genetics/*metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
OTO - NOTNLM
OT  - AMPK
OT  - Deuterohemin-betaAla-His-Thr-Val-Glu-Lys
OT  - PI3K/AKT
OT  - insulin resistance
OT  - type 2 diabetes mellitus
EDAT- 2020/06/09 06:00
MHDA- 2021/01/01 06:00
CRDT- 2020/06/09 06:00
PHST- 2020/05/19 00:00 [received]
PHST- 2020/06/04 00:00 [revised]
PHST- 2020/06/05 00:00 [accepted]
PHST- 2020/06/09 06:00 [pubmed]
PHST- 2021/01/01 06:00 [medline]
PHST- 2020/06/09 06:00 [entrez]
AID - 225199 [pii]
AID - 10.1042/BCJ20200402 [doi]
PST - ppublish
SO  - Biochem J. 2020 Jun 26;477(12):2363-2381. doi: 10.1042/BCJ20200402.