PMID- 24478398
OWN - NLM
STAT- MEDLINE
DCOM- 20140806
LR  - 20211203
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 63
IP  - 4
DP  - 2014 Apr
TI  - Hypothalamic nesfatin-1/NUCB2 knockdown augments hepatic gluconeogenesis that is 
      correlated with inhibition of mTOR-STAT3 signaling pathway in rats.
PG  - 1234-47
LID - 10.2337/db13-0899 [doi]
AB  - Nesfatin-1, an 82-amino acid neuropeptide, has recently been characterized as a 
      potent metabolic regulator. However, the metabolic mechanisms and signaling steps 
      directly associated with the action of nesfatin-1 have not been well delineated. 
      We established a loss-of-function model of hypothalamic nesfatin-1/NUCB2 
      signaling in rats through an adenoviral-mediated RNA interference. With this 
      model, we found that inhibition of central nesfatin-1/NUCB2 activity markedly 
      increased food intake and hepatic glucose flux and decreased glucose uptake in 
      peripheral tissue in rats fed either a normal chow diet (NCD) or a high-fat diet 
      (HFD). The change of hepatic glucose fluxes in the hypothalamic nesfatin-1/NUCB2 
      knockdown rats was accompanied by increased hepatic levels of 
      glucose-6-phosphatase and PEPCK and decreased insulin receptor, insulin receptor 
      substrate 1, and AKT kinase phosphorylation. Furthermore, knockdown of 
      hypothalamic nesfatin-1 led to decreased phosphorylation of mammalian target of 
      rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) 
      and the subsequent suppressor of cytokine signaling 3 levels. These results 
      demonstrate that hypothalamic nesfatin-1/NUCB2 plays an important role in glucose 
      homeostasis and hepatic insulin sensitivity, which is, at least in part, 
      associated with the activation of the mTOR-STAT3 signaling pathway.
FAU - Wu, Dandong
AU  - Wu D
AD  - Department of Endocrinology, Second Affiliated Hospital, and Key Laboratory of 
      Laboratory Medical Diagnostics (Ministry of Education), Chongqing Medical 
      University, Chongqing, China.
FAU - Yang, Mengliu
AU  - Yang M
FAU - Chen, Yang
AU  - Chen Y
FAU - Jia, Yanjun
AU  - Jia Y
FAU - Ma, Zhongmin Alex
AU  - Ma ZA
FAU - Boden, Guenther
AU  - Boden G
FAU - Li, Ling
AU  - Li L
FAU - Yang, Gangyi
AU  - Yang G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140129
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Insulin)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nucb1 protein, rat)
RN  - 0 (Nucleobindins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.9 (Glucose-6-Phosphatase)
RN  - EC 4.1.1.32 (Phosphoenolpyruvate Carboxykinase (GTP))
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Calcium-Binding Proteins/*genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Diet, High-Fat
MH  - Eating
MH  - Gene Knockdown Techniques
MH  - Gluconeogenesis/*drug effects
MH  - Glucose/metabolism
MH  - Glucose Clamp Technique
MH  - Glucose-6-Phosphatase/metabolism
MH  - Hypothalamus/metabolism
MH  - Injections, Intraventricular
MH  - Insulin/physiology
MH  - Liver/*metabolism
MH  - Male
MH  - Nerve Tissue Proteins/*genetics
MH  - Nucleobindins
MH  - Phosphoenolpyruvate Carboxykinase (GTP)/metabolism
MH  - Rats
MH  - STAT3 Transcription Factor/*antagonists & inhibitors/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
EDAT- 2014/01/31 06:00
MHDA- 2014/08/07 06:00
CRDT- 2014/01/31 06:00
PHST- 2014/01/31 06:00 [entrez]
PHST- 2014/01/31 06:00 [pubmed]
PHST- 2014/08/07 06:00 [medline]
AID - db13-0899 [pii]
AID - 10.2337/db13-0899 [doi]
PST - ppublish
SO  - Diabetes. 2014 Apr;63(4):1234-47. doi: 10.2337/db13-0899. Epub 2014 Jan 29.