Neutralization by Insulin of the Hypertensive Effect of Dermcidin Isoform 2: An Environmentally Induced Diabetogenic and Hypertensive Protein

Abstract

The effect of dermcidin isoform 2 (dermcidin), an environmentally induced stress protein, was investigated on the genesis of diabetes mellitus and hypertension, the two major atherosclerotic risk factors. The role of dermcidin as an atherosclerotic risk factor related to the impaired systemic insulin level was investigated. Dermcidin was prepared by electrophoresis using plasma from the subjects with acute ischemic heart disease. Injection of 0.2 μM dermcidin in mice increased the blood glucose level from 98 ± 2.45 mg/dL to 350 ± 10.2 mg/dL which was normalized by the oral administration of acetyl salicylic acid (aspirin) after 24 h. Hypertensive subjects with systolic and diastolic blood pressure of 165 mm and 95 mm of Hg, respectively, had plasma dermcidin level of 95 nM. Ingestion of acetyl salicylic acid (aspirin) (150 mg/70 kg body weight) decreased the systolic and diastolic pressures to 125 mm and 80 mm of Hg, respectively, with decrease of dermcidin level to 15 nM. Incubation of kidney cortex cells with 0.2 μM dermcidin-inhibited synthesis of (r)-cortexin, an antihypertensive protein, and the basal (r)-cortexin level was reduced from 33 nM to 15 nM. Addition of 25 μunits of insulin/mL was found to reverse the inhibition of cortexin synthesis. The effect of dermcidin as a diabetogenic and a hypertensive agent could be controlled either by aspirin or by insulin.

Dermcidin isoform-2 induced nullification of the effect of acetyl salicylic acid in platelet aggregation in acute myocardial infarction

“…We have reported before the appearance of a novel stress induced protein, identified to be dermcidin in the circulation in ACS 14 . Dermcidin was reported to be a potent inhibitor of all known forms of nitric oxide syntheses (NOS) and its systemic synthesis was determined to be due to the expression of dermcidin gene induced by environmental risk factors like tobacco extract or nicotine or alcohol or hypoxia 18 . As such, the appearance of dermcidin in the circulation of ACS was not a “metabolic expression” of the environmental stresses leading to the pathogenesis of the condition, but these environmental factors were actually capable of expressing the dermcidin gene in leucocytes, muscle, endothelial 18 and in hepatic cells and in the whole animal 19 .…”

“…This protein nullified the effect of aspirin induced inhibition of platelet aggregation through the synthesis of prostaglandin. Where NO produce from aspirin 22 , neutralizes the effect of dermcidin, as such the inhibition of aggregation of platelet by asprin has no effect in the inhibition of atherosclerosis, but inhibit the effect of dermcidin by the control of hypertension and hyperglycemia 18 .…”

Accelerated Generation of Extra-Islet Insulin-Producing Cells in Diabetic Rats, Treated with Sodium Phthalhydrazide

“…Non-diabetic healthy mammals’ extra-islet IPCs constitute from 3% [ 9 ] to 15% [ 10 ] of all IPCs in the pancreas. Considering the fundamental importance of insulin in both physiologically normal and pathological conditions [ 11 , 12 , 13 ], among which one of the main is diabetes mellitus, it is not surprising that the phenomenon of insulin synthesis in structures not adapted for this in the traditional sense is a keen area of interest. However, sources, mechanisms, and conditions for the generation of extra-islet IPCs remain poorly understood.…”

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].…”