Impaired insulin-induced platelet antiaggregating effect in obesity and in obese NIDDM patients.
To investigate the effects of insulin on platelets in obesity and in non-insulin-dependent diabetes mellitus (NIDDM)--classic insulin-resistant states--we determined ADP-induced platelet aggregation and platelet cGMP (guanosine 3',5'-cyclic monophosphate) content in platelet-rich plasma obtained from nine obese subjects and nine age-matched healthy volunteers and from eight NIDDM obese patients and nine age-matched healthy volunteers after a 3-min incubation with human recombinant insulin (0, 240, 480, 960, and 1,920 pmol/l). Platelet aggregation was evaluated using different ADP doses to measure the ADP concentration determined on the basis of a dose-response curve necessary to elicit a maximal aggregation of 50% (ED50). Insulin induced a dose-dependent decrease of platelet aggregation to ADP (P = 0.0001) in healthy subjects. A significant effect was evident starting from an insulin concentration of 240 pmol/l. On the contrary, in insulin-resistant subjects, insulin reduced platelet sensitivity to ADP only at a concentration of 1,920 pmol/l. When ADP ED50 values obtained in platelet-rich plasma incubated with insulin were expressed in percentage of the ADP ED50 values obtained in platelet-rich plasma without insulin, considered as 100%, we observed that ADP ED50 with 1,920 pmol/l insulin was 153.6 +/- 13.2% in the younger healthy subject group (P = 0.004), 150.0 +/- 3.8% in the older healthy subject group (P = 0.0001), 116.1 +/- 6.1% in obese subjects (P = 0.031), and 120.0 +/- 8.6% in NIDDM patients (P = 0.05). In healthy subjects, insulin induced a dose-dependent increase of platelet cGMP (P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Trovati
M
M
Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
Mularoni
E M
EM
Burzacca
S
S
Ponziani
M C
MC
Massucco
P
P
Mattiello
L
L
Piretto
V
V
Cavalot
F
F
Anfossi
G
G
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000097:blood*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D000244:Adenosine Diphosphate; D002784:Cholesterol; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D007328:Insulin; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D014280:Triglycerides