Nitric oxide-dependent soluble guanylate cyclase activity is decreased in platelets from male NIDDM patients

To elucidate the underlying mechanisms of platelet dysfunction in diabetes mellitus, we examined the activity of soluble guanylate cyclase (sGC), a key enzyme in the nitric oxide (NO)-related signalling pathway, in platelets from NIDDM (non-insulin dependent diabetes mellitus) patients. The sGC activity was determined by measuring the amount of cyclic GMP produced in platelet cytosol. In the first study, we investigated the platelet sGC activity in untreated NIDDM patients without diabetic complications. In the male NIDDM patients, sodium nitroprusside (SNP) caused a significantly lower sGC response than that in age-matched control male subjects, while the enzyme activity of female diabetics did not differ from that in the controls. Secondly, we investigated effects of diabetic-associated factors on the enzyme activity in the male NIDDM patients. There was no difference in the SNP-stimulated sGC activity in platelets from male diabetics between with and without retinopathy. In the male diabetic patients with retinopathy, however, the platelet sGC activity was slightly increased by treatment with insulin. Interestingly, the changes in enzyme activity did not correlate with plasma glycosylated hemoglobin A1c levels in diabetic patients. The impairment of the NO-related signalling pathway may contribute to the platelet dysfunction observed in patients with diabetes mellitus.