title: Selective insulin resistance affecting nitric oxide release but not plasminogen activator inhibitor-1 synthesis in fibroblasts from insulin-resistant individuals.
abstract: OBJECTIVE
  Insulin activates several processes potentially dangerous for the arterial wall and hyperinsulinemia might be atherogenic. However, other insulin effects are protective for the vessel wall and thus anti-atherogenic. Aim of this study was to investigate whether insulin effects on potentially pro-atherogenic and anti-atherogenic processes were differently affected in cells from insulin-resistant individuals.
  
  
  RESULTS
  We determined insulin effect on nitric oxide (NO) production and plasminogen activator inhibitor (PAI)-1 synthesis in 12 fibroblast strains obtained from skin biopsy samples of 6 insulin-sensitive (IS) (clamp M >7 mg/kg body weight per minute) and 6 insulin-resistant (IR) (clamp M <5 mg/kg body weight per minute) healthy volunteers. Insulin effects on NO release and Akt phosphorylation were significantly impaired in fibroblasts from IR as compared with IS individuals. Conversely, there was not any difference between IR and IS strains in insulin ability to increase PAI-1 antigen levels and, after 24-hour insulin incubation, PAI-1 mRNA increase in IR strains was only slightly less than in IS strains. Insulin ability to induce MAPK activation was also comparable in IR and IS cells.
  
  
  CONCLUSIONS
  We conclude that in cells from IR individuals, insulin action on anti-atherogenic processes, such as NO release, is impaired, whereas the hormone ability to stimulate atherogenic processes, such as PAI-1 release, is preserved.
authors.affiliation: Aging Research Center, Ce.S.I., Gabriele D'Annunzio University Foundation, Chieti-Pescara, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Pandolfi
authors.forename: Anna
authors.initials: A
authors.lastname: Solini
authors.forename: Giuliana
authors.initials: G
authors.lastname: Pellegrini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Mincione
authors.forename: Sara
authors.initials: S
authors.lastname: Di Silvestre
authors.forename: Paola
authors.initials: P
authors.lastname: Chiozzi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Giardinelli
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Di Marcantonio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piccirelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Capani
authors.forename: Agostino
authors.initials: A
authors.lastname: Consoli
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000378:metabolism*; D002478:Cells, Cultured; D003470:Culture Media; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000493:pharmacokinetics; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012694:Serine / Q000378:metabolism
chemical_list: D003470:Culture Media; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D009569:Nitric Oxide; D012694:Serine; D006003:Glycogen; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose