Reduced membrane fluidity in platelets from diabetic patients.
Platelets from diabetic patients are hypersensitive to agonists in vitro. Membrane fluidity modulates cell function, and reduced membrane fluidity in cholesterol-enriched platelets is associated with platelet hypersensitivity to agonists, including thrombin. Decreased membrane fluidity of these platelets is attributed to an increased cholesterol-phospholipid molar ratio in platelet membranes. We examined the response of platelets from diabetic subjects to thrombin, platelet membrane fluidity, and platelet cholesterol-phospholipid molar ratio. Twelve poorly controlled diabetic subjects were compared with 12 age- and sex-matched control subjects. In response to a low concentration of thrombin, mean values for release of [14C]serotonin from washed prelabeled platelets were not significantly different between diabetic and control subjects, but in 8 of 12 diabetic subjects, the release response was greater than in their paired control subjects. Mean steady-state fluorescence polarization values in 1,6-diphenyl-1,3,5-hexatriene-labeled platelets prepared from diabetic subjects were significantly greater than in control subjects; this indicates a decreased membrane fluidity in platelets from diabetic subjects. Total or very-low-density (VLDL), low-density (LDL), or high-density (HDL2, HDL3) lipoprotein cholesterol concentrations in plasma were not significantly different between groups; however, the ratio of VLDL + LDL to HDL2 + HDL3 was significantly greater in diabetic than in control subjects. There was no difference in the total platelet cholesterol-phospholipid molar ratio between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Winocour
P D
PD
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Bryszewska
M
M
Watala
C
C
Rand
M L
ML
Epand
R M
RM
Kinlough-Rathbone
R L
RL
Packham
M A
MA
Mustard
J F
JF
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D002784:Cholesterol / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008560:Membrane Fluidity / Q000502:physiology*; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood
D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010743:Phospholipids