PMID- 18192543
OWN - NLM
STAT- MEDLINE
DCOM- 20080425
LR  - 20131121
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 57
IP  - 4
DP  - 2008 Apr
TI  - Homocysteine upregulates resistin production from adipocytes in vivo and in 
      vitro.
PG  - 817-27
LID - 10.2337/db07-0617 [doi]
AB  - OBJECTIVE: Homocysteine (Hcy) is epidemiologically related to insulin resistance, 
      which has been speculated to be a low-grade systemic inflammatory condition. 
      Resistin acts as a critical mediator of insulin resistance associated with 
      inflammatory conditions. We aimed to determine whether Hcy can induce insulin 
      resistance by directly regulating the expression and secretion of resistin from 
      adipose tissue. RESEARCH DESIGN AND METHODS: The effect of Hcy on the expression 
      and secretion of resistin and insulin resistance was investigated using primary 
      rat adipocytes and mice with hyperhomocysteinemia (HHcy). RESULTS: Hcy impaired 
      glucose transport and, particularly, the insulin signaling pathway as shown by 
      decreased insulin-stimulated tyrosine phosphorylation of insulin receptor and 
      insulin receptor substrate (IRS)-1, increased serine phosphorylation of IRS-1, 
      and inhibited Akt phosphorylation both in vitro and in vivo, and these 
      impairments were accompanied by an increase in resistin expression. Compared with 
      normal mice, HHcy mice with a clinically relevant level of plasma Hcy (19 
      micromol/l) showed significantly increased resistin production from adipose 
      tissue (33.38 +/- 3.08 vs. 19.27 +/- 1.71 ng/ml, P < 0.01). Hcy (300-1000 
      micromol/l) also increased mRNA expression of resistin in primary rat adipocytes 
      in a time- and concentration-dependent manner, with maximal induction at 24 h of 
      approximately fourfold with 1,000 micromol/l. In addition, Hcy-induced resistin 
      expression attenuated by treatment with reactive oxygen species (ROS) scavengers, 
      protein kinase C (PKC), and nuclear factor (NF)-kappaB inhibitors implies a role 
      in the process for ROS, PKC, and NF-kappaB. CONCLUSIONS: HHcy may promote insulin 
      resistance through the induction of resistin expression and secretion from 
      adipocytes via the activation of the ROS-PKC-NF-kappaB pathway.
FAU - Li, Yin
AU  - Li Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Beijing, China
FAU - Jiang, Changtao
AU  - Jiang C
FAU - Xu, Guoheng
AU  - Xu G
FAU - Wang, Nanping
AU  - Wang N
FAU - Zhu, Yi
AU  - Zhu Y
FAU - Tang, Chaoshu
AU  - Tang C
FAU - Wang, Xian
AU  - Wang X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080111
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (NF-kappa B)
RN  - 0 (Resistin)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Adipocytes/cytology/drug effects/*metabolism
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Epididymis
MH  - Gene Expression Regulation
MH  - Homocysteine/*pharmacology
MH  - Hyperhomocysteinemia/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Protein Kinase C/metabolism
MH  - Resistin/*genetics
EDAT- 2008/01/15 09:00
MHDA- 2008/04/26 09:00
CRDT- 2008/01/15 09:00
PHST- 2008/01/15 09:00 [pubmed]
PHST- 2008/04/26 09:00 [medline]
PHST- 2008/01/15 09:00 [entrez]
AID - db07-0617 [pii]
AID - 10.2337/db07-0617 [doi]
PST - ppublish
SO  - Diabetes. 2008 Apr;57(4):817-27. doi: 10.2337/db07-0617. Epub 2008 Jan 11.