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

Adela R, Nethi SK, Bagul PK, Barui AK, Mattapally S, Kuncha M, Patra CR, Reddy PN, Banerjee SK - PLoS ONE (2015)

Bottom Line: 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 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.In conclusion, high NO levels were observed in South Indian diabetic patients.

View Article: PubMed Central - PubMed

Affiliation: Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.

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.

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.

No MeSH data available.


Related in: MedlinePlus

A. iNOS mRNA expression in HUVEC cells after 4hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM. **p<0.01 vs Control. B. iNOS mRNA expression in HUVEC cells after 8hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM.*p<0.05 vs Control. C. eNOS mRNA expression in HUVEC cells after 4hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM. ***p<0.001 vs Control. D. eNOS mRNA expression in HUVEC cells after 8hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM.* p<0.05,**p<0.01 vs Control.
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pone.0125270.g005: A. iNOS mRNA expression in HUVEC cells after 4hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM. **p<0.01 vs Control. B. iNOS mRNA expression in HUVEC cells after 8hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM.*p<0.05 vs Control. C. eNOS mRNA expression in HUVEC cells after 4hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM. ***p<0.001 vs Control. D. eNOS mRNA expression in HUVEC cells after 8hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM.* p<0.05,**p<0.01 vs Control.

Mentions: To find out the mechanism of increased NO levels in HUVEC cells after the exposure to high glucose concentration, we measured iNOS and eNOS gene expression. Significant (p<0.05) increase in iNOS gene expression was observed in HUVEC cells after 4 hours (25mM) and 8 hours (10- and 25mM) of glucose exposure (Fig 5A and 5B). Similarly, eNOS gene expression was increased significantly (p<0.05) after 4 hours (25mM) and 8 hours (10, 25 and 50mM) of glucose exposure (Fig 5C and 5D).


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

Adela R, Nethi SK, Bagul PK, Barui AK, Mattapally S, Kuncha M, Patra CR, Reddy PN, Banerjee SK - PLoS ONE (2015)

A. iNOS mRNA expression in HUVEC cells after 4hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM. **p<0.01 vs Control. B. iNOS mRNA expression in HUVEC cells after 8hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM.*p<0.05 vs Control. C. eNOS mRNA expression in HUVEC cells after 4hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM. ***p<0.001 vs Control. D. eNOS mRNA expression in HUVEC cells after 8hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM.* p<0.05,**p<0.01 vs Control.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4403926&req=5

pone.0125270.g005: A. iNOS mRNA expression in HUVEC cells after 4hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM. **p<0.01 vs Control. B. iNOS mRNA expression in HUVEC cells after 8hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM.*p<0.05 vs Control. C. eNOS mRNA expression in HUVEC cells after 4hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM. ***p<0.001 vs Control. D. eNOS mRNA expression in HUVEC cells after 8hrs treatment of D-Glucose (10, 25, 50mM). Data were represented as mean ± SEM.* p<0.05,**p<0.01 vs Control.
Mentions: To find out the mechanism of increased NO levels in HUVEC cells after the exposure to high glucose concentration, we measured iNOS and eNOS gene expression. Significant (p<0.05) increase in iNOS gene expression was observed in HUVEC cells after 4 hours (25mM) and 8 hours (10- and 25mM) of glucose exposure (Fig 5A and 5B). Similarly, eNOS gene expression was increased significantly (p<0.05) after 4 hours (25mM) and 8 hours (10, 25 and 50mM) of glucose exposure (Fig 5C and 5D).

Bottom Line: 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 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.In conclusion, high NO levels were observed in South Indian diabetic patients.

View Article: PubMed Central - PubMed

Affiliation: Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.

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.

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.

No MeSH data available.


Related in: MedlinePlus