Intracellular molecular effects of insulin resistance in patients with metabolic syndrome.
OBJECTIVE
Patients with metabolic syndrome (MetS) have an increased risk of cardiovascular disease. Data obtained from muscle biopsies have demonstrated altered insulin signaling (IS) in patients with MetS. The IS regulates critical cell functions including molecular-regulated cellular metabolite fluxes, protein and energetic metabolism, cell proliferation and apoptosis with consequent regulation of cell life including endothelial homeostasis and blood coagulation. However, little is known about blood cell IS in MetS patients. The aim of this study was to develop a method to evaluate IS in peripheral lymphocytes to identify altered intracellular molecules in patients with MetS to use as risk biomarkers of vascular thrombosis.


METHODS
We investigated 40 patients with MetS and 20 controls. MetS was defined according to guidelines from the US National Cholesterol Education Program Adult Treatment Panel III. Blood samples were taken from all participants. Total mononuclear cells were isolated from peripheral blood using density gradient centrifugation. IS molecules were evaluated using Western blot analysis followed by computer-assisted densitometer evaluation.


RESULTS
Lymphocytes of MetS patients showed a reduced mTOR expression (the mammalian target of rapamycin) which is a fundamental molecule of IS. Major impairment of IS was confirmed by reduced upstream and downstream mTOR molecules which regulate fundamental cells metabolic functions.


CONCLUSIONS
In patients with MetS, we found a reduction of mTOR and other mTOR-related molecules involved in insulin resistance, cell repair, coagulation and vasculogenesis. A reduced expression of mTOR may reflect an increased risk of vascular thrombosis.
Pasini
Evasio
E
Salvatore Maugeri Foundation, IRCCS, Medical Center of Lumezzane, Brescia, Italy.
Flati
Vincenzo
V
Paiardi
Silvia
S
Rizzoni
Damiano
D
Porteri
Enzo
E
Aquilani
Roberto
R
Assanelli
Deodato
D
Corsetti
Giovanni
G
Speca
Silvia
S
Rezzani
Rita
R
De Ciuceis
Carolina
C
Agabiti-Rosei
Enrico
E
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D018797:Cell Cycle Proteins; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology* / Q000378:metabolism*; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism; D015995:Prevalence; D011972:Receptor, Insulin / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; C546842:MTOR protein, human; D011972:Receptor, Insulin; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
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