Selective insulin resistance affecting nitric oxide release but not plasminogen activator inhibitor-1 synthesis in fibroblasts from insulin-resistant individuals.
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.
Pandolfi
Assunta
A
Aging Research Center, Ce.S.I., Gabriele D'Annunzio University Foundation, Chieti-Pescara, Italy.
Solini
Anna
A
Pellegrini
Giuliana
G
Mincione
Gabriella
G
Di Silvestre
Sara
S
Chiozzi
Paola
P
Giardinelli
Annalisa
A
Di Marcantonio
Maria Carmela
MC
Piccirelli
Alessandro
A
Capani
Fabio
F
Consoli
Agostino
A
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
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