DECREASED ACTIVITY OF ARACHIDONATE 12-LIPOXYGENASE IN PLATELETS OF JAPANESE PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

To study the metabolism of the platelet 12-lipoxygenase pathway in dia betes, we evaluated the correlation between the activity and amount of arachidonate 12-lipoxygenase in the platelets of patients with non-in sulin-dependent-diabetes mellitus (NIDDM). There were four parts in th is investigation: (1) examination of abnormalities in platelet 12-lipo xygenase in patients with NIDDM recruited from the Hospital of Juntend o University School of Medicine; (2) comparison of 12-lipoxygenase in the platelets of non-obese NIDDM patients without angiopathy versus no rmal subjects matched for age, sex, and body mass index (BMI); (3) eva luation of gender differences; and (4) assessment of the potential inf luence of glycemic control. The activity of 12-lipoxygenase was assaye d by incubation of [1-C-14]arachidonic acid with the platelet cytosol. The reaction mixture was extracted and separated by thin-layer chroma tography, and the radioactive end products were detected. The activity of 12-lipoxygenase in the platelets of patients with NIDDM was signif icantly less than in normal subjects (P < .003), whereas the amount of 12-lipoxygenase protein did not differ between the two groups. Thus, the specific activity of 12-lipoxygenase in diabetic patients was sign ificantly less than that of normal subjects (P < .001). The enzyme act ivity and the specific enzyme activity of 12-lipoxygenase in non-obese NIDDM patients without angiopathy were significantly lower than the v alues in normal subjects matched for gender, age, and BMI (P < .006 an d P < .0007, respectively). No significant difference in the activity or amount of platelet 12-lipoxygenase was observed between males and f emales matched for age, BMI, and disease. In addition, no relationship was observed between 12-lipoxygenase activity and blood glucose level s measured at the time of specimen collection. However, slight negativ e correlations were noted between 12-lipoxygenase activity and 1,5-anh ydroglucitol, hemoglobin A(1c) (HbA(1c)), and fructosamine (r = .369, -.354, and -.279, respectively). When recombinant 12-lipoxygenase was incubated with varying concentrations of glucose or fructose, enzyme i nactivation was related to the length of incubation, and was unaffecte d by glucose or fructose. These observations suggest that the activity of 12-lipoxygenase in the platelets of patients with NIDDM is decreas ed by prolonged hyperglycemia. The mechanism involved requires further investigation. Copyright (C) 1998 by W.B. Saunders Company.