PMID- 19815588
OWN - NLM
STAT- MEDLINE
DCOM- 20100105
LR  - 20181201
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Linking)
VI  - 204
IP  - 1
DP  - 2010 Jan
TI  - NO-1886 suppresses diet-induced insulin resistance and cholesterol accumulation 
      through STAT5-dependent upregulation of IGF1 and CYP7A1.
PG  - 47-56
LID - 10.1677/JOE-09-0278 [doi]
AB  - Insulin resistance and dyslipidemia are both considered to be risk factors for 
      metabolic syndrome. Low levels of IGF1 are associated with insulin resistance. 
      Elevation of low-density lipoprotein cholesterol (LDL-C) concomitant with 
      depression of high-density lipoprotein cholesterol (HDL-C) increase the risk of 
      obesity and type 2 diabetes mellitus (T2DM). Liver secretes IGF1 and catabolizes 
      cholesterol regulated by the rate-limiting enzyme of bile acid synthesis from 
      cholesterol 7alpha-hydroxylase (CYP7A1). NO-1886, a chemically synthesized 
      lipoprotein lipase activator, suppresses diet-induced insulin resistance with the 
      improvement of HDL-C. The goal of the present study is to evaluate whether 
      NO-1886 upregulates IGF1 and CYP7A1 to benefit glucose and cholesterol 
      metabolism. By using human hepatoma cell lines (HepG2 cells) as an in vitro 
      model, we found that NO-1886 promoted IGF1 secretion and CYP7A1 expression 
      through the activation of signal transducer and activator of transcription 5 
      (STAT5). Pretreatment of cells with AG 490, the inhibitor of STAT pathway, 
      completely abolished NO-1886-induced IGF1 secretion and CYP7A1 expression. 
      Studies performed in Chinese Bama minipigs pointed out an augmentation of plasma 
      IGF1 elicited by a single dose administration of NO-1886. Long-term 
      supplementation with NO-1886 recovered hyperinsulinemia and low plasma levels of 
      IGF1 suppressed LDL-C and facilitated reverse cholesterol transport by decreasing 
      hepatic cholesterol accumulation through increasing CYP7A1 expression in 
      high-fat/high-sucrose/high-cholesterol diet minipigs. These findings indicate 
      that NO-1886 upregulates IGF1 secretion and CYP7A1 expression to improve insulin 
      resistance and hepatic cholesterol accumulation, which may represent an 
      alternative therapeutic avenue of NO-1886 for T2DM and metabolic syndrome.
FAU - Li, Qinkai
AU  - Li Q
AD  - Key Laboratory for Atherosclerology of Hunan Province, Institute of 
      Cardiovascular Research, Life Science Research Center, University of South China, 
      Hengyang, Hunan 421001, People's Republic of China.
FAU - Yin, Weidong
AU  - Yin W
FAU - Cai, Manbo
AU  - Cai M
FAU - Liu, Yi
AU  - Liu Y
FAU - Hou, Hongjie
AU  - Hou H
FAU - Shen, Qingyun
AU  - Shen Q
FAU - Zhang, Chi
AU  - Zhang C
FAU - Xiao, Junxia
AU  - Xiao J
FAU - Hu, Xiaobo
AU  - Hu X
FAU - Wu, Qishisan
AU  - Wu Q
FAU - Funaki, Makoto
AU  - Funaki M
FAU - Nakaya, Yutaka
AU  - Nakaya Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091008
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Benzamides)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Dietary Fats)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (STAT5 Transcription Factor)
RN  - 133208-93-2 (4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.14.14.23 (Cholesterol 7-alpha-Hydroxylase)
SB  - IM
MH  - *Animal Feed
MH  - Animals
MH  - Benzamides/administration & dosage/*pharmacology
MH  - Cell Line, Tumor
MH  - Cholesterol/administration & dosage/*metabolism
MH  - Cholesterol 7-alpha-Hydroxylase/*metabolism
MH  - Cholesterol, HDL/blood
MH  - Cholesterol, LDL/blood
MH  - Dietary Fats/administration & dosage
MH  - Drug Administration Schedule
MH  - Humans
MH  - Hyperglycemia/etiology/prevention & control
MH  - Hyperinsulinism/blood
MH  - Hypolipidemic Agents/administration & dosage/*pharmacology
MH  - *Insulin Resistance
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Organophosphorus Compounds/administration & dosage/*pharmacology
MH  - STAT5 Transcription Factor/*metabolism
MH  - Swine
MH  - Swine, Miniature
MH  - Up-Regulation
EDAT- 2009/10/10 06:00
MHDA- 2010/01/06 06:00
CRDT- 2009/10/10 06:00
PHST- 2009/10/10 06:00 [entrez]
PHST- 2009/10/10 06:00 [pubmed]
PHST- 2010/01/06 06:00 [medline]
AID - JOE-09-0278 [pii]
AID - 10.1677/JOE-09-0278 [doi]
PST - ppublish
SO  - J Endocrinol. 2010 Jan;204(1):47-56. doi: 10.1677/JOE-09-0278. Epub 2009 Oct 8.