Decreased activity and impaired induction of nitric oxide synthase by lipopolysaccharides in streptozotocin-induced diabetic rats

Khandelwal, Ramji L.; Gupta, Dhananjay; Sulakhe, Prakash V.

doi:10.1016/s0304-4165(03)00005-9

Cited by 9 publications

(7 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High levels of NO production have also been observed in type-2 diabetic subjects [11] and in animal models of diabetes [19]. In contrast, studies have also reported either little or no impact of diabetes on NOS activity in the rat liver and heart [13]. Rats treated with alloxan demonstrated reduced NO generation [20], an effect also observed by Koo and Vaziri [21] for STZinduced diabetic rats.…”

Section: Discussionmentioning

confidence: 87%

“…Khandelwal et al [13] report that diabetes causes either no change or a decrease in cNOS activity in the rat liver accompanied by impairment of iNOS induction by lipopolysaccharides. However, it is not established if the activity of iNOS is altered or if the induction of diabetes is associated with a corresponding increase or decrease in iNOS protein expression.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inducible Nitric Oxide Synthase Activity and Expression in Liver and Hepatocytes of Diabetic Rats

Madar

Kalet-Litman

Stark³

2005

Pharmacology

View full text Add to dashboard Cite

Inducible nitric oxide synthase (iNOS) is expressed by the liver in a number of physiological and pathophysiological conditions. The aim of this study was to investigate the relationship between the diabetic state, iNOS and oxidative stress in the rat liver and isolated hepatocytes. Hepatic iNOS expression and activity was measured in both healthy and streptozotocin-induced diabetic rats and determined in hepatocytes in the presence and absence of insulin. Cu/Zn superoxide dismutase (SOD) and phosphatidylinositol-3-kinase (PI3K) were also measured. In a separate experiment lasting 3 weeks, diabetic rats received either no treatment, two daily injections of insulin or aminoguanidine in the drinking water. Diabetes led to increased activity (45%) and expression (70%) of liver iNOS, an effect that was attenuated by insulin treatment both in vitro and in whole animals. Hepatocyte iNOS expression increased by 56%. Hepatic SOD expression was elevated in the diabetic state, but activity levels were similar to healthy controls. Insulin treatment in vivo led to increased enzyme activity but expression was not modified. Levels of PI3K protein were significantly lower in diabetic rats while insulin treatment markedly increased expression. Aminoguanidine did not inhibit hepatic iNOS in this study. Glycemic control via insulin administration was able to downregulate enhanced hepatic iNOS activity and expression in the liver observed in the diabetic state and improve SOD activity, responses that can potentially reduce the free radical damage associated with diabetes.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Inducible Nitric Oxide Synthase Activity and Expression in Liver and Hepatocytes of Diabetic Rats

Madar

Kalet-Litman

Stark³

2005

Pharmacology

View full text Add to dashboard Cite

show abstract

“…The ability of glucose or glycosylation products to decrease enzymatic activityhas been demonstrated previously in other NOS isoforms in various experimental settings. For example, in SH-SY5Y human neuroblastomacells, Shindo et al [34] demonstrated that elevated D -glucose levels diminish basal NO-dependent cGMP production Recently, Khandelwal et al [35] demonstrated reduced NOS activity in the diabetic rat heart 1 or 12 weeks after STZ injection. However, other studies reported contradictory findings [36, 37].…”

Section: Discussionmentioning

confidence: 99%

Role of Renal Nitric Oxide Synthase in Diabetic Kidney Disease during the Chronic Phase of Diabetes

Khamaisi¹,

Keynan²,

Bursztyn³

et al. 2006

Nephron Physiol

View full text Add to dashboard Cite

Background: Several studies have suggested that an early increase in renal nitric oxide (NO) production or activity mediates pathophysiologic and morphologic changes in diabetic nephropathy. To evaluate the role of NO in developing diabetic kidney disease, we studied the NO system in streptozotocin (STZ)-induced diabetic rats for a period of 8 weeks. Methods: Control rats, STZ-induced diabetic rats, and STZ-induced diabetic rats treated with insulin were monitored and sacrificed at 1, 2, and 8 weeks. Urinary cGMP was measured, and the levels and activity of NO synthase (NOS) isoforms in the kidney cortex were determined at specific times by immunoblotting and diaphorase staining. Results: Diabetic rats had increased kidney weight, urinary volume, glucose, sodium and potassium excretion, which was precluded by insulin treatment. Creatinine clearance was increased in the diabetic group and reversed by insulin treatment. Urinary cGMP decreased by 71, 93, and 92% at 1, 2, and 8 weeks of diabetes, respectively, compared with the control animals. Insulin treatment curtailed the urinary cGMP reduction in diabetic animals. Total NOS activity in the renal cortex was reduced by 65, 52, and 44% after 1, 2, and 8 weeks of diabetes, respectively, and returned to normal levels upon insulin treatment. NADPH diaphorase staining of renal cortical slices showed a 77, 63, and 70% decrease in neuronal NOS isoform activity in the macula densa after 1, 2, and 8 weeks of diabetes, respectively, compared with control non-diabetic animals. This reduction was normalized by insulin treatment. Endothelial NOS protein expression in the kidney cortex tended to increase after 1 week of diabetes and its level was elevated significantly after 2 and 8 weeks of diabetes. However, neuronal NOS protein expression in the kidney cortex was reduced by 52% in 2-week diabetic animals, but this reduction was normalized by insulin treatment. Conclusions: The decreased renal NOS activity during the late phase of diabetes is partially associated with a decrease in neuronal NOS activity and protein expression in kidney macula densa.

show abstract

“…Accordingly, macrophages rather CD4 T cells activated due to an autoimmune reason damage islet cells of the pancreas by causing large amounts of NO release. Khandelwal et al (15) stated that synthesis of different isoforms of nitric oxide synthase enzyme may be increased or reduced depending on age, type of tissue and metabolic changes caused by diabetes in the tissue.…”

Section: Resultsmentioning

confidence: 99%

Measurement of asymmetric dimethylarginine, nitric oxide levels and total antioxidant capacity in experimcntal diabetic rats

Sürmeli¹,

Tekeli²,

Kiral³

2017

Medycyna Weterynaryjna

View full text Add to dashboard Cite

The aim of this study is to investigate the status of oxidative stress and nitric oxide related parameters in diabetic rats. In experimental animals (12 rats) diabetes was induced by intraperitoneal injection of a single 50 mg/kg dose of streptozotocin. At the end of the experiment, in the blood serum of the control and experimental animals ADMA, NO was measured by using ELISA test. Serum levels of GSH, MDA and ceruloplasmin as well as TAC were detected in all animals. Compared to the control animals serum MDA levels in diabetic rats were remarkably and significantly (P<0.05) higher (26.38±1.94 µmol/L and 42.23±1.24 µmol/L, respectively). On the other hand, a statistically significant (P<0.05) decrease from 4.39±0.15 mg/dl to 4.00±0.09 mg/dl was detected in serum GSH levels of the diabetic rats. Compared to the serum ceruloplasmin levels of healthy rats (35.05±2.79 mg/dl), diabetic rats showed a significant decrease (P<0.001) in their serum ceruloplasmin concentration (23.10±1.65 mg/dl). Likewise, serum ADMA concentration of experimental animals (7.26±0.86 ng/ml) was higher than that of controls (5.59±0.75 ng/ml) but not significantly (P>0.05). As to serum TAC, compared to the control rats a statistically significant (P<0.05) decline was observed in diabetic rats. Serum TAC of diabetic rats reduced from 1.01±0.06 mmol trolox equivalent/L to 0.87±0.03 mmol trolox equivalent/L. Serum NO concentration of experimental animals (30.42±2.48 µM/ml) was significantly (P<0.05) less than that of controls (62.28±10.74 µM/ml).

show abstract

Decreased activity and impaired induction of nitric oxide synthase by lipopolysaccharides in streptozotocin-induced diabetic rats

Cited by 9 publications

References 39 publications

Inducible Nitric Oxide Synthase Activity and Expression in Liver and Hepatocytes of Diabetic Rats

Inducible Nitric Oxide Synthase Activity and Expression in Liver and Hepatocytes of Diabetic Rats

Role of Renal Nitric Oxide Synthase in Diabetic Kidney Disease during the Chronic Phase of Diabetes

Measurement of asymmetric dimethylarginine, nitric oxide levels and total antioxidant capacity in experimcntal diabetic rats

Contact Info

Product

Resources

About