Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia

Khalifi, Saeedeh; Rahimipour, Ali; Jeddi, Sajad; Ghanbari, Mahboubeh; Kazerouni, Faranak; Ghasemi, Asghar

doi:10.1016/j.niox.2014.11.011

Cited by 77 publications

(65 citation statements)

References 49 publications

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“…Therefore, we tested whether oral nitrate supplementation lowers arterial pressure in sunitinib‐treated rats. We found that nitrate administered at a dose that effectively lowers arterial pressure in rats with states of low NO availability such as sodium chloride‐induced hypertension,21 senescence,22 diabetes mellitus,31 and in spontaneously hypertensive rats32 did not mitigate sunitinib‐induced hypertension. Furthermore, nitrate supplementation did not affect arterial pressure in controls, which is in agreement with findings by others showing that nitrate administration to healthy 3‐month‐old rats is without significant effects on arterial pressure 22.…”

Section: Discussionmentioning

confidence: 89%

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Witte

Mühlbauer

Braun

et al. 2018

JAHA

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BackgroundThe tyrosine kinase inhibitor sunitinib causes hypertension associated with reduced nitric oxide (NO) availability, elevated renal vascular resistance, and decreased fractional sodium excretion. We tested whether (1) nitrate supplementation mitigates sunitinib‐induced hypertension and NO contributes less to renal vascular resistance as well as fractional sodium excretion regulation in sunitinib‐treated rats than in controls; and (2) renal soluble guanylate cyclase (sGC) is downregulated and sGC activation lowers arterial pressure in rats with sunitinib‐induced hypertension.Methods and ResultsArterial pressure responses to nitrate supplementation and the effects of systemic and intrarenal NO synthase (NOS) inhibition on renal hemodynamics and fractional sodium excretion were assessed in sunitinib‐treated rats and controls. Renal NOS and sGC mRNA as well as protein abundances were determined by quantitative polymerase chain reaction and Western blot. The effect of the sGC activator cinaciguat on arterial pressure was investigated in sunitinib‐treated rats. Nitrate supplementation did not mitigate sunitinib‐induced hypertension. Endothelium‐dependent reductions in renal vascular resistance were similar in control and sunitinib‐treated animals without and with systemic NOS inhibition. Selective intrarenal NOS inhibition lowered renal medullary blood flow in control but not in sunitinib‐treated rats without significant effects on fractional sodium excretion. Renal cortical sGC mRNA and sGC α1‐subunit protein abundance were less in sunitinib‐treated rats than in controls, and cinaciguat effectively lowered arterial pressure by 15‐20 mm Hg in sunitinib‐treated rats.ConclusionsRenal cortical sGC is downregulated in the presence of intact endothelium‐dependent renal vascular resistance regulation in developing sunitinib‐induced hypertension. This suggests that sGC downregulation occurs outside the renal vasculature, increases renal sodium retention, and contributes to nitrate resistance of sunitinib‐induced hypertension.

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Section: Discussionmentioning

confidence: 89%

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Witte

Mühlbauer

Braun

et al. 2018

JAHA

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“…However, STZ-NA-induced diabetic rats, as a model for nonobese type 2 diabetes, do not display insulin resistance, which is the main characteristic of type 2 diabetes. 15,17 In this study, we defined diabetes using a blood glucose cutoff level of 126 mg/dL because the STZ-NA model of type 2 diabetes is associated with moderate hyperglycemia. 17 This value, when determined during fasting, is adopted in human studies to define diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that dietary nitrate prevents an increase in systolic blood pressure and serum glucose, improves glucose tolerance, and restores dyslipidemia in STZ-NA-induced diabetic rats. 15 Jiang et al. 33 have reported that dietary nitrite (50 mg/L for 4 weeks) in db/db diabetic mice improves insulin signaling through GLUT4 translocation to the membrane.…”

Section: Discussionmentioning

confidence: 99%

“…11 We have also previously reported that chronic treatment with a low nitrate dose attenuates oxidative stress in STZ-NA-induced diabetic rats by increasing serum total antioxidant capacity and catalase activity. 15 …”

Section: Discussionmentioning

confidence: 99%

“…12 Recent investigations in animals indicate that dietary nitrate/nitrite has beneficial effects in diabetes and could increase pancreatic blood flow and insulin secretion, 13 and improve both insulin resistance 14 and glucose tolerance. 15 Nitrate/nitrite has protective effects against myocardial ischemia-reperfusion (IR) injury in healthy animals. 6,16 However, no studies have addressed to date the effects of nitrate on myocardial IR injury in diabetes.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Nitrate Intake on Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

Jeddi¹,

Khalifi²,

Ghanbari³

et al. 2016

Arquivos Brasileiros De Cardiologia

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BackgroundCoronary artery disease is 2-3 times more common in diabetic individuals. Dietary nitrate/nitrite has beneficial effects in both diabetes and cardiovascular disease. It also has protective effects against myocardial ischemia-reperfusion (IR) injury in healthy animals. However, the effects of nitrate on myocardial IR injury in diabetic rats have not yet been investigated.ObjectiveWe examined the effects of dietary nitrate on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats.MethodRats were divided into four groups (n=7 in each group): control, control+nitrate, diabetes, and diabetes+nitrate. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Nitrate (sodium nitrate) was added to drinking water (100 mg/L) for 2 months. The hearts were perfused in a Langendorff apparatus at 2 months and assessed before (baseline) and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP), minimum and maximum rates of pressure change in the left ventricle (±dP/dt), endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression, and levels of malondialdehyde (MDA) and NO metabolites (NOx).ResultsRecovery of LVDP and ±dP/dt was lower in diabetic rats versus controls, but almost normalized after nitrate intake. Diabetic rats had lower eNOS and higher iNOS expression both at baseline and after IR, and dietary nitrate restored these parameters to normal values after IR. Compared with controls, heart NOx level was lower in diabetic rats at baseline but was higher after IR. Diabetic rats had higher MDA levels both at baseline and after IR, which along with heart NOx levels decreased following nitrate intake.ConclusionDietary nitrate in diabetic rats provides cardioprotection against IR injury by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart.

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Anti‐obesity effects of Beta vulgaris and Eruca sativa‐based extracts

Markou,

Katsouda,

Papaioannou

et al. 2024

Phytotherapy Research

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Obesity is a major source of morbidity worldwide with more than 2 billion adults being overweight or obese. The incidence of obesity has tripled in the last 50 years, leading to an increased risk for a variety of noncommunicable diseases. Previous studies have demonstrated the positive effects of green leafy vegetables on weight gain and obesity and have attributed these beneficial properties, at least in part, to nitrates and isothiocyanates. Nitrates are converted to nitric oxide (NO) and isothiocyanates are known to release hydrogen sulfide (H2S). Herein, we investigated the effect of extracts and fractions produced from Beta vulgaris and Eruca sativa for their ability to limit lipid accumulation, regulate glucose homeostasis, and reduce body weight. Extracts from the different vegetables were screened for their ability to limit lipid accumulation in adipocytes and hepatocytes and for their ability to promote glucose uptake in skeletal muscle cultures; the most effective extracts were next tested in vivo. Wild type mice were placed on high‐fat diet for 8 weeks to promote weight gain; animals receiving the selected B. vulgaris and E. sativa extracts exhibited attenuated body weight. Treatment with extracts also led to reduced white adipose tissue depot mass, attenuated adipocyte size, reduced expression of Dgat2 and PPARγ expression, and improved liver steatosis. In contrast, the extracts failed to improve glucose tolerance in obese animals and did not affect blood pressure. Taken together, our data indicate that extracts produced from B. vulgaris and E. sativa exhibit anti‐obesity effects, suggesting that dietary supplements containing nitrates and sulfide‐releasing compounds might be useful in limiting weight gain.

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Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia

Cited by 77 publications

References 49 publications

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

Effects of Nitrate Intake on Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

Anti‐obesity effects of Beta vulgaris and Eruca sativa‐based extracts

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