Abstract
Endothelin-I (ET-I) is one of the potent vasoconstrictors secreted from endothelial cells when needed. Many studies revealed the elevation of serum ET-I with human diabetes and microangiopathies. Since insulin resistance is a case of mixed diabetic and pre-diabetic cases, many risk factors beyond obesity and inflammation are proposed. The current study aims to demonstrate the association between serum ET-I and asymmetric dimethylarginine (ADMA) and insulin resistance in type 2 diabetes mellitus (T2DM). Sera of 73 subjects were enrolled currently (control= 35 subjects, and 38 with T2DM for more than 7 years), aged (40-60) years old, with distinct body mass index (BMI) ≤ 25 for control volunteers and (BMI) ≥ 25 for obesity and diabetes patients. Peripheral serum ET-I and ADMA levels were significantly (P≤ 0.0001) higher in T2DM than the control subjects. Receiver operating characteristic curve analysis regarded ET-I and ADMA as good markers for T2DM disease and insulin resistance, correlations between ET-I and anthropometrics revealed a strong increase of urotensin-II (UII), ADMA, homeostatic model assessment for insulin resistance (HOMA-IR) and hemoglobin A1C (HbA1C) with an increase of ET-I. These results are supported by the data of multiple regression analysis, showing that HOMA-IR, HbA1C, UII, BMI, and mean arterial pressure (MAP) are related to ET-I independently. The endothelin-I and ADMA had a positive relationship with increase insulin resistance and may serve as prognostic and diagnostic clinical biomarkers of insulin resistance. Collectively, Therefore, these measurements could evaluate the incidence of DM, and help to better rise up the knowledge about the progression of DM complications.
Highlights
Endothelin-I (ET-1) is one of the potent vasoconstrictors synthesized and secreted from endothelial cells of vasculatures1
ET-I correlated strongly to most of the parameters mentioned before with p
According to data illustrated in Fig, 1, ROC curves, serum ET-I concentrations are significantly higher in DM patients and both diabetes and non-diabetes groups were compared using t-test, the area under the curve in females was slightly higher than males but the total AUC was 0.9117 with a 0.0001 significant level
Summary
Endothelin-I (ET-1) is one of the potent vasoconstrictors synthesized and secreted from endothelial cells of vasculatures. Endothelin-I (ET-1) is one of the potent vasoconstrictors synthesized and secreted from endothelial cells of vasculatures1 This argumentative vasoconstrictor is still under debate through its vast effects and diverse pathways of action, ET-I has been implicated in the progression of diabetes mellitus 2 and cardiovascular diseases (CVD), through endothelial dysfunction 3, 4. According to Muniyappa et al 10 insulin has a pivotal role in regulating vascular tone through increasing endothelial NO synthase production (eNOS) and secretion of ET-I through the myosin-activated protein kinase (MAPK) pathway. There is an established relationship between increased ADMA levels and insulin resistance regarding obesity in patients with DM 12. No studies have investigated the relationship between ET-I, and ADMA with insulin resistance, this case-control study aims to establish the relation between ET-I and ADMA in insulin-resistant subjects
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