Reverse Correlation between Urine Nitric Oxide Metabolites and Insulin Resistance in Patients with Type 2 Diabetes Mellitus.

Kurioka, Soichi; Koshimura, Kunio; Murakami, Yoshio; Nishiki, Masateru; Kato, Yuzuru

doi:10.1507/endocrj.47.77

Cited by 32 publications

(18 citation statements)

References 22 publications

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“…There is increasing evidence that NO synthesis and the vasodilating properties of insulin are impaired in insulin resistant states, such as Type II diabetes and obesity [31,32]. Thus, our data agree with previous findings [33]. In the 301 Type II diabetic patients, the mutant group of -786T-C polymorphism showed a higher HbA 1c than the non-mutant group.…”

Section: Discussionsupporting

confidence: 92%

Association of - 786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance

et al. 2002

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Aims/hypothesis. Endothelial derived nitric oxide synthase (eNOS) gene polymorphisms affect eNOS activity and are associated with abnormal vasomotility and impaired local blood flow. A decrease in local blood flow has been reported to cause insulin resistance. The aim of this study was to examine a possible association of two eNOS polymorphisms, Glu298Asp (G894T) in exon 7 and -786T-C mutation with insulin resistance. Methods. Genotypes of both Glu298Asp and -786T-C mutation were examined by the PCR-RFLP method. Plasma nitrate and nitrite concentrations were also measured. Results. The allele frequencies of both polymorphisms showed no considerable differences in 233 non-diabetic subjects and 301 patients with Type II (non-insulin-dependent) diabetes mellitus. Non-diabetic subjects with the -786C allele had (p<0.05) higher fasting plasma insulin and homeostasis model assessment of insulin resistance than those with the -786T/ -786T genotype. Diabetic subjects with -786C allele showed higher HbA 1c than those with the -786T/ -786T genotype. A euglycaemic hyperinsulinemic clamp study done on 71 of the 301 patients showed a lower glucose infusion rate in diabetic patients with the -786C allele than those without it. In diabetic patients with the -786C allele, plasma nitrate and nitrite concentrations were lower than in subjects without it (p=0.026). No differences were observed between mutant carriers of Glu298Asp and non-carriers among both nondiabetic subjects and Type II diabetic patients. Conclusions/interpretation. The -786T-C mutation of the eNOS gene is associated with insulin resistance in both Japanese non-diabetic subjects and Type II diabetic patients. [Diabetologia (2002[Diabetologia ( ) 45:1594[Diabetologia ( -1601 Keywords Endothelial nitric oxide synthase, polymorphism, glucose infusion rate, homeostasis model assessment of insulin resistance insulin resistance, intima-media thickness. Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita City, Japan a key role in the regulation of vascular tone. Skeletal muscle glucose uptake is enhanced by insulin-mediated vasodilation and the decrease in local blood flow can result in insulin resistance [1][2][3][4][5]. However, several reports deny a major role of endothelial NO production in determining insulin sensitivity [6,7].Recently eNOS knockout mice have been reported to be insulin resistant [8]. These mice have also shown a decrease in whole-body and muscle-glucose uptake as well as the simultaneous decrease in the local blood flow [9]. Two major polymorphisms have been found in the human eNOS gene: Glu298Asp (G894T) in exon 7 and -786T-C mutation in the 5′-flanking region. Glu298Asp causes a structural change of the eNOS Endothelial derived nitric oxide (NO), synthesized from L-arginine by the endothelium isoform of NO synthase (eNOS), mediates local vasodilation and plays

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Section: Discussionsupporting

confidence: 92%

Association of - 786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance

et al. 2002

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“…24 Second, the ischemic damage can be further amplified by insulin resistance that has been related to a lower ability of insulin to induce vasodilatation through impaired nitric oxide endothelial production or accelerated inactivation. 25 The relationship between DR and cardiovascular autonomic function has been examined in earlier studies using HRV analysis. 26,27 Schmidt et al 26 have shown that DR is associated with heart rate response by electrocardiographical monitoring in type 2 diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Diabetic retinopathy is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients

et al. 2009

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Diabetic retinopathy (DR) and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. This preliminary study was therefore designed to test the hypothesis that DR is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients without insulin treatment. Seventy persons were diagnosed to have type 2 diabetes in the examination from June 2004 to May 2006. The study group consisted of 29 type 2 diabetic patients with DR (age: 58 ± 6 years, mean ± s.d.) and 41 type 2 diabetic patients with no DR (NDR) (n¼41, 58 ± 5 years). Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability, plasma norepinephrine concentration and cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphic findings. DR patients had lower BRS, early and delayed 123 I-MIBG myocardial uptake values and higher percent washout rate (WR) of 123 I-MIBG than the NDR patients. With respect to metabolic findings, DR patients had higher fasting plasma insulin concentration (Po0.0001) and higher homeostasis model assessment (HOMA) index (Po0.00001) than the NDR patients. Multiple logistic regression analysis revealed that the presence of DR was independently predicted by HOMA index and the percent WR of 123 I-MIBG (Po0.01 and Po0.05, respectively). Our results suggest that DR is associated with depressed cardiovascular autonomic function and insulin resistance and that HOMA index and the percent WR of 123 I-MIBG are independently associated with DR in Japanese patients with type 2 diabetes mellitus.

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“…The differ- ence in NO production between our results and the previous report may be due to rat strain or the period of experiment. Insulin resistance was expected to be enhanced by the change of leptin, TNF-a and NO [12,18,32,33]. To evaluate insulin resistance, we used the HOMA-R, which is well correlated with M-values obtained by euglycemic hyperinsulinemic clamp [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

“…An increase in NO production observed in rats following exercise training has been known to improve insulin resistance and leptin resistance in diabetes mellitus and obesity [32]. Urinary NO excretion decreases in parallel with the progression of insulin resistance in human type 2 diabetes [33]. Therefore, NO is suggested to be related to the pathogenesis of diabetes.…”

mentioning

confidence: 99%

The Effect of Leptin, Tumor Necrosis Factor-α (TNF-α), and Nitric Oxide (NO) Production on Insulin Resistance in Otsuka Long-Evans Fatty Rats

2003

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Abstract. Adipocytokines and nitric oxide (NO) play important roles in type 2 diabetes; however, the regulatory mechanism has not been fully clarified. To investigate the role of adipocytokines and NO production on insulin resistance in type 2 diabetes, the LETO rats and the OLETF rats were fed a control diet or a high-fat diet for 4 weeks. After 4 weeks the blood levels of leptin, tumor necrosis factor-a (TNF-a), and NO were measured. As an indicator of insulin resistance, the homeostasis model assessment for insulin resistance (HOMA-R) was applied. Food intake in high-fat diet group rats was lower than in control diet group rats. The high fat diet increased body weight (BW), but did not significantly affect the HOMA-R and blood pressure (BP). Leptin and TNF-a levels were significantly higher in the OLETF rats than in the LETO rats, while NO levels did not change between the two groups. The high-fat diet elevated blood leptin levels, but not TNF-a and NO levels. The HOMA-R in the OLETF rats was correlated with leptin, but not with BP, BW, TNF-a or NO. NO showed an inverse correlation with BP. In conclusion, leptin, TNF-a, and NO may each regulate insulin sensitivity through their own unique pathways. The elucidation of the regulatory mechanism of adipocytokines and NO may give a clue to clarify the pathophysiology of insulin resistance.

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Reverse Correlation between Urine Nitric Oxide Metabolites and Insulin Resistance in Patients with Type 2 Diabetes Mellitus.

Cited by 32 publications

References 22 publications

Association of - 786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance

Association of - 786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance

Diabetic retinopathy is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients

The Effect of Leptin, Tumor Necrosis Factor-α (TNF-α), and Nitric Oxide (NO) Production on Insulin Resistance in Otsuka Long-Evans Fatty Rats

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Reverse Correlation between Urine Nitric Oxide Metabolites and Insulin Resistance in Patients with Type 2 Diabetes Mellitus.

Cited by 32 publications

References 22 publications

Association of - 786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance

Association of - 786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance

Diabetic retinopathy is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients

The Effect of Leptin, Tumor Necrosis Factor-&alpha; (TNF-&alpha;), and Nitric Oxide (NO) Production on Insulin Resistance in Otsuka Long-Evans Fatty Rats

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The Effect of Leptin, Tumor Necrosis Factor-α (TNF-α), and Nitric Oxide (NO) Production on Insulin Resistance in Otsuka Long-Evans Fatty Rats