PMID- 19053948
OWN - NLM
STAT- MEDLINE
DCOM- 20090316
LR  - 20111117
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 418
IP  - 3
DP  - 2009 Mar 15
TI  - Insulin resistance in polycystic ovary syndrome is associated with defective 
      regulation of ERK1/2 by insulin in skeletal muscle in vivo.
PG  - 665-71
LID - 10.1042/BJ20082176 [doi]
AB  - Insulin resistance is a recognized feature of PCOS (polycystic ovary syndrome). 
      However, the molecular reason(s) underlying this reduced cellular insulin 
      sensitivity is not clear. The present study compares the major insulin signalling 
      pathways in skeletal muscle isolated from PCOS and controls. We measured 
      whole-body insulin sensitivity and insulin signalling in skeletal muscle biopsies 
      taken before and after acute exposure to hyperinsulinaemia in nine women 
      diagnosed with PCOS and seven controls. We examined the expression, basal 
      activity and response to in vivo insulin stimulation of three signalling 
      molecules within these human muscle samples, namely IRS-1 (insulin receptor 
      substrate-1), PKB (protein kinase B) and ERK (extracellular-signal-regulated 
      kinase) 1/2. There was no significant difference in the expression, basal 
      activity or activation of IRS-1 or PKB between PCOS and control subjects. 
      However, there was a severe attenuation of insulin stimulation of the ERK pathway 
      in muscle from all but two of the women with PCOS (the two most obese), and an 
      accompanying trend towards higher basal phosphorylation of ERK1/2 in PCOS. These 
      results are striking in that the metabolic actions of insulin are widely believed 
      to require the IRS-1/PKB pathway rather than ERK, and the former has been 
      reported as defective in some previous PCOS studies. Most importantly, the 
      molecular defect identified was independent of adiposity. The altered response of 
      ERK to insulin in PCOS was the most obvious signalling defect associated with 
      insulin resistance in muscle from these patients.
FAU - Rajkhowa, Madhurima
AU  - Rajkhowa M
AD  - Biomedical Research Institute, Department of Obstetrics and Gynaecology, 
      Ninewells Hospital, Dundee, Scotland, U.K.
FAU - Brett, Sandra
AU  - Brett S
FAU - Cuthbertson, Daniel J
AU  - Cuthbertson DJ
FAU - Lipina, Christopher
AU  - Lipina C
FAU - Ruiz-Alcaraz, Antonio J
AU  - Ruiz-Alcaraz AJ
FAU - Thomas, Giles E
AU  - Thomas GE
FAU - Logie, Lisa
AU  - Logie L
FAU - Petrie, John R
AU  - Petrie JR
FAU - Sutherland, Calum
AU  - Sutherland C
LA  - eng
GR  - CZB/4/125/Chief Scientist Office/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Insulin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Adult
MH  - Female
MH  - Humans
MH  - Insulin/*physiology
MH  - Insulin Resistance/*physiology
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/*metabolism
MH  - Muscle, Skeletal/*enzymology
MH  - Polycystic Ovary Syndrome/*physiopathology
EDAT- 2008/12/05 09:00
MHDA- 2009/03/17 09:00
CRDT- 2008/12/05 09:00
PHST- 2008/12/05 09:00 [pubmed]
PHST- 2009/03/17 09:00 [medline]
PHST- 2008/12/05 09:00 [entrez]
AID - BJ20082176 [pii]
AID - 10.1042/BJ20082176 [doi]
PST - ppublish
SO  - Biochem J. 2009 Mar 15;418(3):665-71. doi: 10.1042/BJ20082176.