PMID- 21289241
OWN - NLM
STAT- MEDLINE
DCOM- 20110630
LR  - 20211020
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 96
IP  - 5
DP  - 2011 May
TI  - Chronically increased S6K1 is associated with impaired IRS1 signaling in skeletal 
      muscle of GDM women with impaired glucose tolerance postpartum.
PG  - 1431-41
LID - 10.1210/jc.2010-2116 [doi]
AB  - CONTEXT: The rapidly increasing prevalence of gestational diabetes mellitus (GDM) 
      globally places a growing population at risk for developing type 2 diabetes 
      mellitus (T2DM), particularly those with persistent impaired glucose tolerance 
      (IGT) postpartum. OBJECTIVE: We sought to 1) identify dynamic insulin signaling 
      abnormalities in vivo in a prospective, longitudinal study of GDM women compared 
      to weight-matched pregnant controls both antepartum and postpartum; and 2) 
      determine abnormalities that might distinguish GDM women who normalize their 
      glucose tolerance postpartum from those with persistent IGT. DESIGN: Skeletal 
      muscle biopsies were obtained before and after a 75-g glucose load in nine 
      overweight to obese GDM women and 10 weight-matched pregnant controls antepartum 
      and postpartum. Postpartum biopsies were collected in five weight-matched GDM 
      women with IGT (GDM/IGT). RESULTS: GDM women had decreased skeletal muscle 
      insulin-stimulated insulin receptor and insulin receptor substrate 1 (IRS1) 
      tyrosine activation and reduced IRS1, concomitant with increased basal IRS1 
      serine phosphorylation and basal p70 S6-kinase (S6K1) activation, which resolved 
      postpartum. However, GDM/IGT subjects had a persistent impairment in IRS1 
      activation and increased S6K1 phosphorylation compared to GDM subjects with 
      normal glucose tolerance. CONCLUSIONS: This study reveals that women with GDM 
      demonstrate impaired IRS1 signaling associated with increased S6K1 activation in 
      skeletal muscle in vivo. This defect is maintained postpartum in GDM/IGT 
      subjects, despite similar body weights and cytokine levels. Given that GDM women 
      with persistent IGT are at a high risk of developing T2DM, understanding how the 
      nutrient-sensitive mammalian target of rapamycin/S6K1 pathway is chronically 
      activated in GDM may lead to important therapies that could prevent the 
      progression to T2DM.
FAU - Barbour, Linda A
AU  - Barbour LA
AD  - Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, 
      University of Colorado Denver, Aurora, Colorado 80045, USA.
FAU - McCurdy, Carrie E
AU  - McCurdy CE
FAU - Hernandez, Teri L
AU  - Hernandez TL
FAU - Friedman, Jacob E
AU  - Friedman JE
LA  - eng
GR  - R01 DK062155/DK/NIDDK NIH HHS/United States
GR  - P30 DK048520/DK/NIDDK NIH HHS/United States
GR  - DK048520-P30/DK/NIDDK NIH HHS/United States
GR  - 1 UL 1 RR 025780/RR/NCRR NIH HHS/United States
GR  - K12 HD057022/HD/NICHD NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
GR  - K23 RR 17496/RR/NCRR NIH HHS/United States
GR  - 5R01DK062155-04/DK/NIDDK NIH HHS/United States
GR  - K23 RR017496/RR/NCRR NIH HHS/United States
GR  - R24 DK090964/DK/NIDDK NIH HHS/United States
GR  - M01 RR000051/RR/NCRR NIH HHS/United States
GR  - M01-RR00051/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110202
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - 452VLY9402 (Serine)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
SB  - IM
MH  - Adult
MH  - Biomarkers/blood
MH  - Blood Glucose/metabolism
MH  - Blotting, Western
MH  - Diabetes, Gestational/genetics/*metabolism/pathology
MH  - Female
MH  - Glucose Intolerance/*genetics/*physiopathology
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Infant, Newborn
MH  - Insulin/physiology
MH  - Insulin Receptor Substrate Proteins/*genetics/*physiology
MH  - Insulin Resistance/genetics/physiology
MH  - Muscle, Skeletal/*metabolism/pathology
MH  - Phosphorylation
MH  - Postpartum Period/genetics
MH  - Pregnancy
MH  - RNA/biosynthesis/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*biosynthesis/*genetics
MH  - Serine/metabolism
MH  - Signal Transduction/physiology
MH  - Tyrosine/metabolism
PMC - PMC3085211
EDAT- 2011/02/04 06:00
MHDA- 2011/07/01 06:00
PMCR- 2012/05/01
CRDT- 2011/02/04 06:00
PHST- 2011/02/04 06:00 [entrez]
PHST- 2011/02/04 06:00 [pubmed]
PHST- 2011/07/01 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - jc.2010-2116 [pii]
AID - 10-2116 [pii]
AID - 10.1210/jc.2010-2116 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2011 May;96(5):1431-41. doi: 10.1210/jc.2010-2116. Epub 
      2011 Feb 2.