Diminished production of thromboxane B2 and prostaglandin E by stimulated polymorphonuclear leukocytes from insulin-treated diabetic subjects.
As an initial step to investigate the possibility that abnormal polymorphonuclear leukocyte (PMNL) function in diabetes might be related to abnormalities of arachidonic acid metabolism, product of the cyclooxygenase pathway were assayed in PMNL from 27 insulin-treated diabetic subjects and 27 age- and sex-matched nondiabetic subjects. It was found that the major prostanoid products formed were thromboxane B2 (TxB2) and prostaglandin E (PGE). Production of both these substances was greatly enhanced in PMNL from control and diabetic subjects by exposure to a killed preparation of Staphylococcus aureus (S. aureus) or to zymosan. There was a marked reduction in the production of TXB2 by PMNL from diabetic subjects in response to stimulation by both S. aureus [670 +/- 98 (SE) versus 1010 +/- 76 pg/10(6) PMNL/90 min, P less than 0.01] and zymosan (583 +/- 53 versus 1034 +/- 46 pg/10(6) PMNL/90 min, P less than 0.001). Similarly, production of PGE was significantly reduced in diabetics in response to both S. aureus (145 +/- 29 versus 232 +/- 16 pg/10(6) PMNL/90 min, P less than 0.05) and zymosan (181 +/- 21 versus 271 +/- 27 pg/10(6) PMNL/90 min, P less than 0.01). There was no relation between the plasma glucose at the time of the test and the production of either prostanoid. Diminished production of cyclooxygenase products of arachidonic acid metabolism should be added to the known abnormalities of PMNL in diabetes. In view of the demonstrated or inferred effects of cyclooxygenase products on aspects of PMNL function, this observation may be important in understanding the pathogenesis of PMNL dysfunction in diabetes.
D001095:Arachidonic Acids / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism; D002469:Cell Separation; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism*; D013211:Staphylococcus aureus; D013929:Thromboxane B2 / Q000378:metabolism*; D013931:Thromboxanes / Q000378:metabolism*; D015054:Zymosan / Q000494:pharmacology
D001095:Arachidonic Acids; D001786:Blood Glucose; D007328:Insulin; D011458:Prostaglandins E; D013931:Thromboxanes; D013929:Thromboxane B2; D015054:Zymosan