title: Insulin resistance in obesity and metabolic syndrome: is there a connection with platelet l-arginine transport?
abstract: OBJECTIVE
  Nitric oxide (NO) is a short-lived gaseous messenger with multiple physiological functions including regulation of blood flow, platelet adhesion and aggregation inhibition. NO synthases (NOS) catalyze the conversion of cationic amino acid L-arginine in L-citrulline and NO. Despite an increasing prevalence of obesity and metabolic syndrome (MetS) in the last decades, the exact mechanisms involved in the pathogenesis and cardiovascular complications are not fully understood. We have examined the effects of obesity and MetS on the L-arginine-NO-cGMP pathway in platelets from a population of adolescents.
  
  
  METHODS
  A total of twenty six adolescent patients (13 with obesity and 13 with MetS) and healthy volunteers (n=14) participated in this study. Transport of L-arginine, NO synthase (NOS) activity and cGMP content in platelets were analyzed. Moreover, platelet function, plasma levels of L-arginine, metabolic and clinical markers were investigated in these patients and controls.
  
  
  RESULTS
  L-arginine transport (pmol/10(9) cells/min) in platelets via system y(+)L was diminished in obese subjects (20.8±4.7, n=10) and MetS patients (18.4±3.8, n=10) compared to controls (52.3±14.8, n=10). The y(+)L transport system correlated negatively to insulin levels and Homeostasis Model Assessment of Insulin Resistance (HOMA IR) index. No differences in NOS activity and cGMP content were found among the groups. Moreover, plasma levels of L-arginine were not affected by obesity or MetS.
  
  
  CONCLUSIONS
  Our study provides the first evidence that obesity and MetS lead to a dysfunction of L-arginine influx, which negatively correlates to insulin resistance. These findings could be a premature marker of future cardiovascular complications during adulthood.
authors.affiliation: Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carmen R L
authors.initials: CR
authors.lastname: Assumpção
authors.forename: Tatiana M C
authors.initials: TM
authors.lastname: Brunini
authors.forename: Natália R
authors.initials: NR
authors.lastname: Pereira
authors.forename: Amélio F
authors.initials: AF
authors.lastname: Godoy-Matos
authors.forename: Mariana A S
authors.initials: MA
authors.lastname: Siqueira
authors.forename: Giovanni E
authors.initials: GE
authors.lastname: Mann
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Mendes-Ribeiro
mesh_terms: D000293:Adolescent; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport; D001792:Blood Platelets / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology; D016022:Case-Control Studies; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP