The impaired synthesis of insulin and its inability to inhibit platelet aggregation in cerebrovascular accident

Abstract

Both ischemic stroke (IS) and hemorrhagic stroke (HS) are reported to occur due to thrombosis on the arteries of the brain. As diabetes mellitus is a risk factor for strokes and insulin is reported to prevent thrombosis, the role of insulin in IS and HS was investigated. Forty eight stroke victims (IS = 22, HS = 26) and equal number of aged and sex matched normal volunteers participated in the study. Nitric oxide was determined by methemoglobin method. Insulin and Dermcidin isoform-2 (DCN2) level was determined by ELISA by using insulin and dermcidin antibody. Insulin binding to the platelet membrane was analyzed by scat chard plot. Treatment of normal platelet rich plasma (10(8)platelets/ml) with 15μUnits insulin/ml produced 1.41 nmol NO. The PRP from the IS and HS victims produced 0.38 nmol NO and 0.08 nmol NO respectively. Pretreatment of PRP from IS or HS subjects with 15 μM aspirin followed by 15μUnits of insulin/ml resensitized the platelets to the inhibitory effect of insulin. Mice hepatocytes treated with 0.14 μM DCN2 abolished the glucose induced insulin synthesis by NO that can be reversed by using 15 μM aspirin. It can be concluded that presence of DCN2 in stroke causes a condition similar to type I diabetes and nullified the effect of insulin in the inhibition of platelet aggregation in both IS and HS. The effect was reversed by 15 μM aspirin.

Insulin resistance in prostate cancer patients and predisposing them to acute ischemic heart disease

“…This stress-induced protein, which was found in the circulation of AMI and ACS patients, was the platelet aggregator and the inhibitor of the aspirin effect through the impairment of nitric oxide [21,22]. We reported from our laboratory that dermcidin-induced hyperglycemia was due to the impairment of NO [44,45] which causes endothelial dysfunction relating to the elevated HbA1c [46,47]. Insulin, which is an anti-thrombotic factor, plays a very important role in the inhibition of AIHD [19,48] through the production of nitric oxide [49] by the expression of eNOS gene [50].…”

“…So, despite the small sample size, it can be assumed from the above found results of clinical experimentation that dermcidin could be one of the responsible factors for the creation of prostate malignancy and concomitantly IR here. Previously, it was found that dermcidin impaired the insulin activity through NO inhibition [22,44] and the found result of elevated HbA1c level and lower level of NO are the indication of endothelial dysfunction which actually precipitates cardiovascular disease. Chest pain is the distinctive feature of AMI and low level of NO might be the causative factor of pain in AMI, and cTroponon is the well known marker of the occurrence of AMI.…”