PMID- 25796170
OWN - NLM
STAT- MEDLINE
DCOM- 20150703
LR  - 20151119
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 285
IP  - 1
DP  - 2015 May 15
TI  - Fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in 
      insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy 
      mice.
PG  - 61-70
LID - S0041-008X(15)00093-9 [pii]
LID - 10.1016/j.taap.2015.03.011 [doi]
AB  - Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) 
      and is characterized by defects in insulin signaling. Protein tyrosine 
      phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling 
      pathways, and its increased activity and expression are implicated in the 
      pathogenesis of insulin resistance. Therefore, the inhibition of PTP1B is 
      anticipated to become a potential therapeutic strategy to treat T2DM. 
      Fumosorinone (FU), a new natural product isolated from insect fungi Isaria 
      fumosorosea, was found to inhibit PTP1B activity in our previous study. Herein, 
      the effects of FU on insulin resistance and mechanism in vitro and in vivo were 
      investigated. FU increased the insulin-provoked glucose uptake in 
      insulin-resistant HepG2 cells, and also reduced blood glucose and lipid levels of 
      type 2 diabetic KKAy mice. FU decreased the expression of PTP1B both in 
      insulin-resistant HepG2 cells and in liver tissues of diabetic KKAy mice. 
      Furthermore, FU increased the phosphorylation of IRbeta, IRS-2, Akt, GSK3beta and 
      Erk1/2 in insulin-resistant HepG2 cells, as well as the phosphorylation of IRbeta, 
      IRS-2, Akt in liver tissues of diabetic KKAy mice. These results showed that FU 
      increased glucose uptake and improved insulin resistance by down-regulating the 
      expression of PTP1B and activating the insulin signaling pathway, suggesting that 
      it may possess antidiabetic properties.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Liu, Zhi-Qin
AU  - Liu ZQ
AD  - College of Life Sciences, Key Laboratory of Medicinal Chemistry and Molecular 
      Diagnosis of Ministry of Education, Hebei University, Baoding 071002, PR China; 
      College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality 
      control of Hebei province, Hebei University, Baoding 071002, PR China.
FAU - Liu, Ting
AU  - Liu T
AD  - College of Life Sciences, Key Laboratory of Medicinal Chemistry and Molecular 
      Diagnosis of Ministry of Education, Hebei University, Baoding 071002, PR China.
FAU - Chen, Chuan
AU  - Chen C
AD  - College of Life Sciences, Key Laboratory of Medicinal Chemistry and Molecular 
      Diagnosis of Ministry of Education, Hebei University, Baoding 071002, PR China.
FAU - Li, Ming-Yan
AU  - Li MY
AD  - College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality 
      control of Hebei province, Hebei University, Baoding 071002, PR China.
FAU - Wang, Zi-Yu
AU  - Wang ZY
AD  - College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality 
      control of Hebei province, Hebei University, Baoding 071002, PR China.
FAU - Chen, Ruo-Song
AU  - Chen RS
AD  - College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality 
      control of Hebei province, Hebei University, Baoding 071002, PR China.
FAU - Wei, Gui-Xiang
AU  - Wei GX
AD  - College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality 
      control of Hebei province, Hebei University, Baoding 071002, PR China.
FAU - Wang, Xiao-Yi
AU  - Wang XY
AD  - College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality 
      control of Hebei province, Hebei University, Baoding 071002, PR China.
FAU - Luo, Du-Qiang
AU  - Luo DQ
AD  - College of Life Sciences, Key Laboratory of Medicinal Chemistry and Molecular 
      Diagnosis of Ministry of Education, Hebei University, Baoding 071002, PR China. 
      Electronic address: duqiangluo999@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150318
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Pyridones)
RN  - 0 (fumosorinone)
RN  - EC 3.1.3.48 (PTPN1 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
RN  - EC 3.1.3.48 (Ptpn1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Biomarkers/blood
MH  - Blood Glucose/drug effects/metabolism
MH  - Diabetes Mellitus/blood/*drug therapy/enzymology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/*pharmacology
MH  - Hep G2 Cells
MH  - Humans
MH  - Hydroxamic Acids/*pharmacology
MH  - Hypoglycemic Agents/*pharmacology
MH  - Insulin/*metabolism
MH  - *Insulin Resistance
MH  - Liver/*drug effects/enzymology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1/*antagonists & 
      inhibitors/metabolism
MH  - Pyridones/*pharmacology
MH  - Signal Transduction/*drug effects
MH  - Time Factors
OTO - NOTNLM
OT  - Diabetes mellitus
OT  - Glucose uptake
OT  - Insulin resistance
OT  - Insulin signaling
OT  - Protein tyrosine phosphatase 1B
EDAT- 2015/03/23 06:00
MHDA- 2015/07/04 06:00
CRDT- 2015/03/23 06:00
PHST- 2014/10/22 00:00 [received]
PHST- 2015/03/03 00:00 [revised]
PHST- 2015/03/10 00:00 [accepted]
PHST- 2015/03/23 06:00 [entrez]
PHST- 2015/03/23 06:00 [pubmed]
PHST- 2015/07/04 06:00 [medline]
AID - S0041-008X(15)00093-9 [pii]
AID - 10.1016/j.taap.2015.03.011 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2015 May 15;285(1):61-70. doi: 
      10.1016/j.taap.2015.03.011. Epub 2015 Mar 18.