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

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

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54 Scopus citations

Abstract

Background We 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. Methods Endothelial 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. Results We 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. Conclusion In 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.

Original languageEnglish (US)
Article numbere125270
JournalPloS one
Volume10
Issue number4
DOIs
StatePublished - Apr 20 2015
Externally publishedYes

Bibliographical note

Funding Information:
SKB is grateful to Department of Biotechnology (DBT) for providing Ramalingaswami Fellowship (BT/HRD/35/02/2006). CRP is grateful to Department of Science and Technology (DST), New Delhi for ‘Ramanujan Fellowship grant’(SR/S2/RJN-04/2010; GAP0305). RA is a scholar in the Fogarty International Center of the National Institutes of Health training program under Award Number D43 TW 009078. SKN is thankful to DST, New Delhi for supporting with junior research fellowship. We are thank full to Gayatri Vishwakarma, who is Bio-statistician, at Clinical Development Services Agency (THSTI) for helping in statistical part. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
Copyright: © 2015 Adela et al.

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