title: Vanadate enhances but does not normalize glucose transport and insulin receptor phosphorylation in skeletal muscle from obese women with gestational diabetes mellitus.
abstract: OBJECTIVE
  We compared the insulin-mimetic effects of vanadate, a protein-tyrosine phosphatase inhibitor, with the effects of insulin on skeletal muscle glucose transport and insulin receptor and insulin receptor substrate 1 phosphorylation to test the hypothesis that protein-tyrosine phosphatases participate in pregnancy-induced insulin resistance.
  
  
  METHODS
  Skeletal muscle fiber strips were obtained from the rectus abdominis during cesarean delivery in 7 patients with gestational diabetes mellitus, 11 pregnant women with normal glucose tolerance (pregnant control group), and 11 nonpregnant women undergoing elective surgery (nonpregnant control group). Muscle tissues were incubated in vitro for 15 to 60 minutes with or without maximal insulin (100 nmol/L) or sodium vanadate (6 micromol/L). Insulin receptor and insulin receptor substrate 1 tyrosine phosphorylation were measured, as was 2-deoxyglucose transport. The levels of protein-tyrosine phosphatase 1B were measured by Western blot analysis.
  
  
  RESULTS
  Vanadate stimulated maximal 2-deoxyglucose transport more than did insulin alone in all samples (P<.05), but the value was still less in muscle tissues from pregnant control subjects and patients with gestational diabetes mellitus (P<.05). In muscle tissues from pregnant control subjects vanadate increased tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 to levels similar to those in muscle tissues from nonpregnant control subjects. In patients with gestational diabetes mellitus vanadate increased insulin receptor and insulin receptor substrate 1 tyrosine phosphorylation, but these values remained less than in muscle tissues from nonpregnant control subjects (P<.05). Protein-tyrosine phosphatase 1B levels were not significantly different in skeletal muscles from each group.
  
  
  CONCLUSIONS
  Vanadate did not restore normal glucose transport activity during pregnancy complicated by gestational diabetes mellitus, which indicates that decreased glucose uptake is probably not caused by impaired tyrosine phosphorylation events alone. Increased serine kinase activity and impaired glucose transporter 4 translocation probably contribute to insulin signaling abnormalities associated with pregnancy, especially in patients with gestational diabetes mellitus.
authors.affiliation: Department of Nutrition, Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shao
authors.forename: P M
authors.initials: PM
authors.lastname: Catalano
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Ishizuka
authors.forename: J E
authors.initials: JE
authors.lastname: Friedman
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D016640:Diabetes, Gestational / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D012016:Reference Values; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D014638:Vanadates; D014443:Tyrosine; D011972:Receptor, Insulin; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D005947:Glucose