Hyperglycaemia enhances nitric oxide production in diabetes: a study from South Indian patients.

Sanjay K Banerjee,Saidulu Mattapally,Susheel Kumar Nethi,Pankaj K Bagul,Ramu Adela,Ayan K Barui,Aldrin V Gomes,Chitta R Patra,Madhusudan Kuncha,P Naveen Chander Reddy

doi:10.1371/journal.pone.0125270

Sanjay K Banerjee, Saidulu Mattapally + Show 8 more

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https://doi.org/10.1371/journal.pone.0125270

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Abstract

BackgroundWe have previously reported that increased glucose levels were associated with higher serum nitric oxide (NO) levels in fructose-fed insulin resistant rats. However, the relationship between hyperglycemia and serum NO level was not clear. Therefore, the present study was designed to find the association between hyperglycemia and serum NO levels in Type 2 diabetic (T2DM) patients and T2DM with cardiovascular complication.MethodsEndothelial cells (HUVEC) were treated with of D-glucose (10-100mM), and NO levels and NOS gene expression was measured. Hyperglycaemia was induced in Sprague-Dawley rats, and serum NO levels were measured after 8 weeks. For clinical evaluation, five groups of patients were recruited: Control (CT, n=48), Type 2 diabetes (T2DM, n=26), T2DM with hypertension (DMHT, n=46), Coronary artery diseases (CAD, n=29) and T2DM with coronary artery diseases (DMCD, n=38). NO (nitrite + nitrate) levels were measured from human serum.ResultsWe found a significant (p<0.05) and dose-dependent increase in NO levels in HUVEC cells after 4 hours of high glucose exposure. eNOS and iNOS gene expression was increased in HUVEC cells after different concentrations and time periods of glucose treatment. We also observed significant (149.1±25μM, p<0.01) increase in serum NO levels in hyperglycaemic rats compared to control (76.6±13.2μM). Serum NO level was significantly higher in T2DM (111.8 μM (81.7-122.4), p<0.001) and DMCD patients ((129.4 μM (121.2-143.5), p <0.001) but not in CAD patients (76.4 μM (70.5-87)), as compared to control (68.2 μM (56.4-82.3)). We found significantly lower NO levels (83.5 μM (60.5-122.9)) in subjects suffering from diabetes since more than 5 years, compared to subjects (115.3 μM (75.2-127.1), p<0.001) with less than 5 years.ConclusionIn conclusion, high NO levels were observed in South Indian diabetic patients. Higher glucose levels in serum might be responsible for activation of endothelial cells to enhance NO levels.

Highlights

Metabolic syndrome is a serious health concern
We found a significant (p
SKN is thankful to Department of Science and Technology (DST), New Delhi for supporting with junior research fellowship

Summary

Introduction

Metabolic syndrome is a serious health concern. In United States, 35% of adults are at high risk of developing cardiovascular diseases, diabetes, stroke, atherosclerosis and coronary artery disease [1]. Number of Type 2 diabetes mellitus (T2DM) patients is increasing in both developed and developing countries but 80% contribution is from low and middle income countries [2]. Increasing incidence of morbidity and mortality due to cardiovascular complications including coronary artery diseases has been observed in Type 2 diabetic patients [3]. Hyperglycaemia and other metabolic changes may lead to impairment of nitric oxide (NO) production [6]. Impairment of endothelial function in T2DM patients leads to cardiovascular diseases. Endothelial dysfunction is the early feature of cardiovascular complications in T2DM [7]. The present study was designed to find the association between hyperglycemia and serum NO levels in Type 2 diabetic (T2DM) patients and T2DM with cardiovascular complication

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