Insulin, but not proinsulin C-peptide, enhances platelet fibrinogen binding in vitro in Type 1 diabetes mellitus patients and healthy subjects.
BACKGROUND
Insulin treatment is essential in Type 1 diabetes mellitus (DM). However, previous studies have shown complex effects of insulin on platelet function. Proinsulin C-peptide has shown beneficial effects in Type 1 DM, but it is not known if it can affect platelet activation. We thus investigated how insulin, C-peptide, and their combination influence platelets from DM patients and healthy subjects.


METHODS
Hirudinized blood from patients (n = 10) and healthy subjects (n = 10) was preincubated in the absence or presence of insulin (10 and 100 microU/ml), C-peptide (0.3, 1, and 10 nM), or the combination (1 nM C-peptide + 100 microU/ml insulin or 10 nM C-peptide + 100 microU/ml insulin) and further incubated without or with 10(-6) M ADP. Platelet activation was monitored by platelet fibrinogen binding and P-selectin expression using whole blood flow cytometry. Data are presented as binding index (BI), which integrates the percentage of activated cells and their mean fluorescence intensity.


RESULTS
Insulin enhanced ADP-induced platelet fibrinogen binding in both Type 1 DM patients and healthy subjects. For example, ADP-stimulated platelet fibrinogen BI increased from 4.25 +/- 0.74 to 8.63 +/- 2.00 with 10 microU/ml insulin (P < .05) in Type 1 DM patients. However, insulin did not increase platelet P-selectin expression. Proinsulin C-peptide did not influence platelet fibrinogen binding or P-selectin expression in either Type 1 DM patients or healthy subjects. The combination of C-peptide and insulin had similar effects as insulin alone.


CONCLUSIONS
Insulin at physiological concentrations enhances platelet fibrinogen binding in both Type 1 DM patients and healthy subjects, whilst C-peptide does not influence platelet activation.
Department of Medicine, Division of Clinical Pharmacology, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Hu
H
Hu
Nailin
N
Li
Karin
K
Ekberg
Bo-Lennart
BL
Johansson
Paul
P
Hjemdahl
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002096:C-Peptide / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis; D010455:Peptides / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D039341:Receptors, Fibrinogen / Q000378:metabolism*; D013268:Stimulation, Chemical
D002096:C-Peptide; D007328:Insulin; D019007:P-Selectin; D010455:Peptides; D039341:Receptors, Fibrinogen; D000244:Adenosine Diphosphate; D005340:Fibrinogen