title: Immunophilins are involved in the altered platelet aggregation observed in patients with type 2 diabetes mellitus.
abstract: Platelet hyperaggregability might contribute to vascular complications associated with type 2 diabetes mellitus (DM2).Experimental evidence supports a direct link between altered Ca(2+) entry and hyperaggregability in DM2 patients.
  
  
  OBJECTIVE
  We aimed to investigate whether altered immunophilin expression and function are involved in the abnormal Ca(2+) entry observed in platelets from DM2 patients.
  
  
  RESULTS
  Inhibition of immunophilins by tacrolimus (FK506) and sirolimus (rapamycin) reduced Ca(2+) entry in platelets from healthy donors and DM2 patients. Similarly, immunophilin inhibitors reduced platelet degranulation in both healthy and DM2 subjects. Nevertheless, α-granule secretion reduction was greater than that observed for dense granules in platelets from DM2 patients. However, no difference was observed in the inhibition of secretion in platelets from healthy subjects. Additionally, altered expression of FK506 binding protein-52 (FKBP52) and coupling to Ca(2+) channels were found in platelets from DM2 patients compared to healthy subjects. Finally, reduction in platelet function from healthy subjects and DM2 patients in the presence of immunophilin antagonists was observed, being this dysfunction more evident in platelets from DM2 patients.
  
  
  CONCLUSIONS
  We suggest that, among others, FKBP52 expression and function are altered in platelets from DM2 patients, contributing to the altered Ca(2+) entry and hyperaggregability in these cells.
authors: Department of Physiology (Phycell group), University of Extremadura, 10003-Cáceres, Spain.
authors: E
authors: E
authors: López
authors: A
authors: A
authors: Berna-Erro
authors: J M
authors: JM
authors: Hernández-Cruz
authors: G M
authors: GM
authors: Salido
authors: P C
authors: PC
authors: Redondo
authors: J A
authors: JA
authors: Rosado
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D020104:Immunophilins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D020104:Immunophilins; D002118:Calcium; D016559:Tacrolimus