Search

Background: Random-pattern skin flaps are commonly used to repair skin tissue defects in surgical tissue reconstruction. However, flap necrosis in the distal area due to ischemia injury is still challenging for its applications in plastic surgery. The complications of diabetes will further increase the risk of infection and necrosis. Methods: This study induced type 2 diabetes mellitus (T2DM) rats with a high-fat diet and STZ. The survival rate of the skin flap was observed by adding inorganic sodium nitrate to drinking water. Histology and immunohistochemistry were used to detect the damage to the skin flap. The nitrate content was measured by total nitric oxide and nitrate/nitrite parameter assay. Dihydroethidium and malondialdehyde (MDA) assays were used to value oxidative stress. Rat colon feces were collected for 16s rRNA gene sequence. Results: Our studies showed that nitrate administration leads to anti-obesity and anti-diabetic effects. Nitrate directly increased the survival area of skin flaps in diabetic rats and mean blood vessel density by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. The 16s rRNA sequence revealed that nitrate may regulate the homeostasis of the gut microbiota and re-store energy metabolism. Conclusion: Dietary nitrate has been shown to maintain the homeostasis of oxidative stress and gut microbiota to promote flap survival in rats with T2DM. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the possible effects of chronic nitrate supplementation on the metabolites of energy metabolism during high-intensity, high-volume intermittent training (HIHVT). In this placebo-controlled double-blind study, 17 participants exercised 3 times a week on a cycle ergometer. Sodium nitrate or sodium chloride as the placebo was supplemented daily at 8.5 mg/kg body weight for 10 days. The training exercise consisted of a warm-up, a 45-min interval period, and a post-exercise period. Oxygen uptake, respiratory exchange ratio, and various parameters were measured in the venous blood and plasma. During training, the oxygen uptake and respiratory exchange ratio did not differ between the nitrate and the placebo group. Venous plasma concentrations of nitrate and nitrite were significantly increased in the nitrate group (p < 0.001 and p = 0.007, respectively). Triglyceride concentrations were significantly lower in the nitrate group than in the placebo group (p = 0.010). The concentration of free fatty acids in the plasma did not change upon nitrate supplementation and no significant differences were observed in the contribution of fat to energy metabolism during exercise. An increase in plasma ammonia concentration was observed in the nitrate group during and after exercise (p = 0.048). Metabolites of energy-rich phosphates did not differ between the nitrate and chloride groups, suggesting no improvement in efficiency through the supplemented nitrate. It was concluded that nitrate supplementation did not reduce oxygen uptake and adenosine triphosphate resynthesis by hydrolysis or through creatine kinase activity during high-intensity, high-volume intermittent exercise. Although, lipid metabolism as well as amino acid metabolism might be affected by nitrate supplementation during HIHVT. [ABSTRACT FROM AUTHOR]

Objective(s): Nitrite, a nitric oxide (NO) donor, increases insulin secretion from pancreatic islets and has positive metabolic effects in type 2 diabetes (T2D). Here, we test the hypothesis of whether nitrite-induced insulin secretion is due to blunting of diabetes-induced oxidative stress in the islets. Materials and Methods: T2D was created in male rats using a combination of streptozotocin at 25 mg/kg and a high-fat diet. Wistar rats were assigned to 3 groups (n=6 in each group), including control, T2D, and T2D+nitrite; the latter group consumed drinking water containing sodium nitrite (50 mg/l) for eight weeks. At the end of the study, mRNA levels of NADPH oxidase (Nox1, 2, 3, and 4), superoxide dismutase (SOD1, 2, and 3), glutathione peroxides (GPX1 and 7), glutathione reductase (GR), catalase, thioredoxin (TXN1 and 2), and thioredoxin reductase (TXNRD1) were measured in the isolated pancreatic islets. Results: In the islets of diabetic rats, mRNA expressions of Nox1, 2, and 4 were higher, whereas expressions of SOD1, 2, catalase, GPX1, 7, GR, and TXN1 were lower than controls. Nitrite significantly (all P-values<0.05) decreased gene expression of Nox1 (0.39-fold) and Nox4 (0.23-fold) and increased gene expression of SOD1 (2.2-fold), SOD2 (2.8-fold), catalase (2.7-fold), GPX1 (2.2- fold), GPX7 (6.0-fold), GR (3.0-fold), TXN1 (2.1-fold), and TXNRD1 (2.3-fold) in diabetic rats. Conclusion: Nitrite decreased oxidative stress in isolated pancreatic islets of rats with T2D by suppressing oxidants and augmenting anti-oxidants. These findings favor the notion that nitriteinduced insulin secretion is partially due to decreased oxidative stress. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes (T2D) is increasing worldwide. Decreased nitric oxide (NO) bioavailability is involved in the pathophysiology of T2D and its complications. L‐citrulline (Cit), a precursor of NO production, has been suggested as a novel therapeutic agent for T2D. Available data from human and animal studies indicate that Cit supplementation in T2D increases circulating levels of Cit and L‐arginine while decreasing circulating glucose and free fatty acids and improving dyslipidemia. The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic β cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and β‐oxidation, and decreased glyceroneogenesis in the adipose tissue. Thus, Cit has antihyperglycemic, antidyslipidemic, and antioxidant effects and has the potential to be used as a new therapeutic agent in the management of T2D. This review summarizes available literature from human and animal studies to explore the effects of Cit on metabolic parameters in T2D. It also discusses the possible mechanisms underlying Cit‐induced improved metabolic parameters in T2D. [ABSTRACT FROM AUTHOR]

Many short-term studies with dietary nitrate supplementation in humans and animal models reported positive effects on the cardiovascular system, exercise efficiency, and immune function. However, there has been long-standing concern related to cancer and adverse hormonal effects. We studied the long-term effects of different potassium nitrate (KNO3) concentrations on laboratory mice longevity and structural changes in their organs. Four groups of male mice were treated with 0 mg (0%), 45 mg (1%), 90 mg (2%), and 140 mg (3%) KNO3 in the drinking water. The groups were monitored for agility and health status daily. The lifespan of mice and organ pathological changes were analyzed. We found no detrimental effects of life-long supplementation of KNO3 on the survival of mice in treatment groups. Nitrate supplementation was associated with a lower level of pathological changes (p = 0.002). We conclude that KNO3 supplementation had no carcinogenic effect on mice and possibly prevented the organs from aging. [ABSTRACT FROM AUTHOR]

Nitrate, a nitric oxide (NO) donor, has antiobesity effect in female rats. This study hypothesized that the antiobesity effect of nitrate in female rats is due to the browning of white adipose tissue (WAT). Female Wistar rats (aged 8 months) were divided into two groups (n = 10/group): the control group received tap water and the nitrate group received water containing 100 mg/L of sodium nitrate for 9 months. At months 0, 3, 6, and 9, obesity indices were measured. At month 9, gonadal adipose tissue was used to measure messenger RNA (mRNA) and protein levels of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), PPAR‐γ coactivator 1‐α (PGC1‐α), uncoupling protein 1 (UCP1), and adipocyte density and area. After the 9‐month intervention, nitrate‐treated rats had lower body weight, body mass index, thoracic circumference, and abdominal circumference by 6.4% (p =.012), 9.1% (p =.029), 6.0% (p =.056), and 5.7% (p =.098), respectively. In addition, nitrate‐treated rats had higher PPAR‐γ (mRNA: 1.78‐fold, p =.016 and protein: 19%, p =.076), PGC1‐α (mRNA: 1.69‐fold, p =.012 and protein: 68%, p =.001), and UCP1 (mRNA: 2.50‐fold, p =.001 and protein: 81%, p =.001) in gonadal adipose tissue. Nitrate also reduced adipocyte area by 35% (p =.054) and increased adipocyte density by 31% (p =.086). In conclusion, antiobesity effect of nitrate in female rats is associated with increased browning of gonadal adipose tissue as indicated by higher expression of PPAR‐γ, PGC1‐α, and UCP1 and reduced adipocyte area and increased adipocyte density. Significance statement: In this study, the effect of nitrate on obesity indices as well as the expression of the genes involved in the browning of white adipose tissue (WAT), including peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), PPAR‐γ coactivator 1‐α (PGC1‐α), and uncoupling protein 1 (UCP1) were measured in female rats. Results indicate that after a 9‐month intervention, nitrate‐treated rats had lower body weight, body mass index, thoracic, and abdominal circumference. In addition, chronic nitrate administration at a low dose increased mRNA and protein levels of PPAR‐γ, PGC1‐α, and UCP1, decreased adipocyte area, and increased adipocyte density in the gonadal adipose tissue. These findings indicate that the antiobesity effect of nitrate is associated with the browning of WAT. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a gas that serves as a ubiquitous signaling molecule participating in physiological activities of various organ systems. Nitric oxide is produced in the endocrine pancreas and contributes to synthesis and secretion of insulin. The potential role of NO in insulin secretion is disputable – both stimulatory and inhibitory effects have been reported. Available data indicate that effects of NO critically depend on its concentration. Different isoforms of NO synthase (NOS) control this and have the potential to decrease or increase insulin secretion. In this review, the role of NO in insulin secretion as well as the possible reasons for discrepant findings are discussed. A better understanding of the role of NO system in the regulation of insulin secretion may facilitate the development of new therapeutic strategies in the management of diabetes. [ABSTRACT FROM AUTHOR]

Beneficial metabolic effects of inorganic nitrate (NO3−) and nitrite (NO2−) in type 2 diabetes mellitus (T2DM) have been documented in animal experiments; however, this is not the case for humans. Although it has remained an open question, the redox environment affecting the conversion of NO3− to NO2− and then to NO is suggested as a potential reason for this lost-in-translation. Ascorbic acid (AA) has a critical role in the gastric conversion of NO2− to NO following ingestion of NO3−. In contrast to AA-synthesizing species like rats, the lack of ability to synthesize AA and a lower AA body pool and plasma concentrations may partly explain why humans with T2DM do not benefit from NO3−/NO2− supplementation. Rats also have higher AA concentrations in their stomach tissue and gastric juice that can significantly potentiate gastric NO2−-to-NO conversion. Here, we hypothesized that the lack of beneficial metabolic effects of inorganic NO3− in patients with T2DM may be at least in part attributed to species differences in AA metabolism and also abnormal metabolism of AA in patients with T2DM. If this hypothesis is proved to be correct, then patients with T2DM may need supplementation of AA to attain the beneficial metabolic effects of inorganic NO3− therapy. [ABSTRACT FROM AUTHOR]