PMID- 24958127
OWN - NLM
STAT- MEDLINE
DCOM- 20150109
LR  - 20220318
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 230
IP  - 1
DP  - 2015 Jan
TI  - Ghrelin augments the expressions and secretions of proinflammatory adipokines, 
      VEGF120 and MCP-1, in differentiated 3T3-L1 adipocytes.
PG  - 199-209
LID - 10.1002/jcp.24699 [doi]
AB  - Ghrelin is a physiological-active peptide with growth hormone-releasing activity, 
      orexigenic activity, etc. In addition, the recent study has also suggested that 
      ghrelin possesses the pathophysiological abilities related with type 2 diabetes. 
      However, the ghrelin-direct-effects implicated in type 2 diabetes on peripheral 
      tissues have been still unclear, whereas its actions on the central nervous 
      system (CNS) appear to induce the development of diabetes. Thus, to assess its 
      peripheral effects correlated with diabetes, we investigated the regulatory 
      mechanisms about adipokines, which play a central role in inducing peripheral 
      insulin resistance, secreted from mature 3T3-L1 adipocytes stimulated with 
      ghrelin in vitro . The stimulation with 50 nmol/L ghrelin for 24 h resulted in 
      the significant 1.9-fold increase on vascular endothelial growth factor-120 
      (VEGF(120)) releases (p < 0.01) and the 1.7-fold on monocyte chemoattractant 
      protein-1 (MCP-1) (p < 0.01) from 3T3-L1 adipocytes, respectively, while ghrelin 
      failed to enhance tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, 
      IL-10 and adiponectin secretions. In addition, Akt phosphorylation on Ser473 and 
      c-Jun NH2 -terminal protein kinase (JNK) phosphorylation on Thr183/Tyr185 were 
      markedly enhanced 1.4-fold (p < 0.01) and 1.6-fold (p < 0.01) in the 
      ghrelin-stimulated adipocytes, respectively. Furthermore, the treatment with 
      LY294002 (50 mumol/L) and Wortmannin (10nmol/L), inhibitors of 
      phosphatidylinositol 3-kinase (PI3K), significantly decreased the amplified 
      VEGF(120) secretion by 29% (p < 0.01) and 28% (p < 0.01) relative to the cells 
      stimulated by ghrelin alone, respectively, whereas these inhibitors had no 
      effects on increased MCP-1 release. On the other hand, JNK inhibitor 
      SP600125 (10 mumol/L) clearly reduced the increased MCP-1, but not VEGF(120), 
      release by 35% relative to the only ghrelin-stimulated cells (p < 0.01). In 
      conclusion, ghrelin can enhance the secretions of proinflammatory adipokines, 
      VEGF(120) and MCP-1, but fails to affect IL-10 and adiponectin which are 
      considered to be anti-inflammatory adipokines. Moreover, this augmented VEGF(120) 
      release is invited through the activation of PI3K pathways and the MCP-1 is 
      through JNK pathways. Consequently, our results strongly suggest that ghrelin can 
      induce the development of diabetes via its direct-action in peripheral tissues as 
      well as via in CNS.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Kitahara, Atsuko
AU  - Kitahara A
AD  - Third Department of Internal Medicine.
FAU - Takahashi, Kazuto
AU  - Takahashi K
FAU - Moriya, Rie
AU  - Moriya R
FAU - Onuma, Hirohisa
AU  - Onuma H
FAU - Handa, Keiko
AU  - Handa K
FAU - Sumitani, Yoshikazu
AU  - Sumitani Y
FAU - Tanaka, Toshiaki
AU  - Tanaka T
FAU - Katsuta, Hidenori
AU  - Katsuta H
FAU - Nishida, Susumu
AU  - Nishida S
FAU - Sakurai, Takuya
AU  - Sakurai T
FAU - Inukai, Kouichi
AU  - Inukai K
FAU - Ohno, Hideki
AU  - Ohno H
FAU - Ishida, Hitoshi
AU  - Ishida H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Adiponectin)
RN  - 0 (Androstadienes)
RN  - 0 (Anthracenes)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromones)
RN  - 0 (Ghrelin)
RN  - 0 (IL10 protein, mouse)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - 130068-27-8 (Interleukin-10)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 3T3 Cells
MH  - AMP-Activated Protein Kinases/antagonists & inhibitors/biosynthesis
MH  - Adipocytes/*drug effects/metabolism
MH  - Adiponectin/biosynthesis
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Anthracenes/pharmacology
MH  - Cell Line
MH  - Chemokine CCL2/*metabolism
MH  - Chromones/pharmacology
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Endoplasmic Reticulum Stress/drug effects
MH  - Ghrelin/*pharmacology
MH  - Interleukin-10/biosynthesis
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Mice
MH  - Morpholines/pharmacology
MH  - Oxidative Stress/drug effects
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Vascular Endothelial Growth Factor A/*metabolism
MH  - Wortmannin
OTO - NOTNLM
OT  - 3T3-L1 adipocytes
OT  - Ghrelin
OT  - Leptin
OT  - MCP-1
OT  - VEGF120
EDAT- 2014/06/25 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/06/25 06:00
PHST- 2014/06/19 00:00 [received]
PHST- 2014/06/11 00:00 [revised]
PHST- 2014/06/18 00:00 [accepted]
PHST- 2014/06/25 06:00 [entrez]
PHST- 2014/06/25 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - 10.1002/jcp.24699 [doi]
PST - ppublish
SO  - J Cell Physiol. 2015 Jan;230(1):199-209. doi: 10.1002/jcp.24699.