title: Hyperglycaemia enhances nitric oxide production in diabetes: a study from South Indian patients.
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 ± 25 μM, p<0.01) increase in serum NO levels in hyperglycaemic rats compared to control (76.6 ± 13.2 μM). 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
authors.forename: Ramu
authors.initials: R
authors.lastname: Adela
authors.affiliation: Biomaterials Group, Lipid Science and Technology Division, Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
authors.forename: Susheel Kumar
authors.initials: SK
authors.lastname: Nethi
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Bagul
authors.affiliation: Biomaterials Group, Lipid Science and Technology Division, Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
authors.forename: Ayan K
authors.initials: AK
authors.lastname: Barui
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
authors.forename: Saidulu
authors.initials: S
authors.lastname: Mattapally
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
authors.forename: Madhusudan
authors.initials: M
authors.lastname: Kuncha
authors.affiliation: Biomaterials Group, Lipid Science and Technology Division, Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
authors.forename: Chitta R
authors.initials: CR
authors.lastname: Patra
authors.affiliation: Cardiology Division, Mediciti Hospital, Hyderabad, 500063, India.
authors.forename: P Naveen Chander
authors.initials: PN
authors.lastname: Reddy
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Banerjee
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D007194:India; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C517652:hemoglobin A1c protein, human