Skip to main content
Top
Published in: Journal of Diabetes & Metabolic Disorders 1/2020

01-06-2020 | Nitrate | Research article

Improving effect of combined inorganic nitrate and nitric oxide synthase inhibitor on pancreatic oxidative stress and impaired insulin secretion in streptozotocin induced-diabetic rats

Authors: Zahra Shabgard Shahraki, Narges Karbalaei, Marzieh Nemati

Published in: Journal of Diabetes & Metabolic Disorders | Issue 1/2020

Login to get access

Abstract

Purpose

The aim of this study was to evaluate the effect of dietary nitrate on secretory function of pancreatic islet and oxidative stress status in streptozotocin (STZ) induced type 1 diabetes in absence or presence of nitric oxide synthase inhibitor (L-NAME).

Methods

Fifty adult male sprague-dawly rats were divided into 5 groups: controls (C), diabetes (D), diabetes+nitrate (DN), diabetes +L-NAME (D + Ln), and diabetes+nitrate+L-NAME (DN + Ln) for 45 days. The concentrations of sodium nitrate and L-NAME were respectively 80 mg/L in drinking water and 5 mg/kg intraperitoneally. Body weight gain, plasma levels of glucose and insulin, islet insulin secretion and content, lipid peroxidation and antioxidant status in the pancreas of rats were determined.

Results

Compared to control group, the body weight gain and plasma insulin level were significantly decreased and plasma glucose and pancreatic NO and MDA concentrations and antioxidant enzymes activities were significantly increased in the STZ diabetic rats. In the diabetic rats, nitrate alone significantly reduced plasma glucose and increased pancreatic SOD and GPx activity. Reduced plasma glucose, pancreatic MDA and NO concentrations and increased plasma insulin level and pancreatic islet insulin secretion were observed in D + Ln and DN + Ln groups. Antioxidant enzymes activities were increased in diabetic rats which received combination of nitrate and L-NAME.

Conclusions

Our results showed that nitrate without effect on pancreatic islet insulin content and secretion decreased the blood glucose and slightly moderate oxidative stress and its effects in the presence of L-NAME on glucose hemostasis and pancreatic insulin secretion higher than those of nitrate alone.
Literature
1.
go back to reference Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008;7(2):156–67.PubMedCrossRef Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008;7(2):156–67.PubMedCrossRef
2.
go back to reference Omar SA, Webb AJ, Lundberg JO, Weitzberg E. Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases. J Intern Med. 2016;279(4):315–36.PubMedCrossRef Omar SA, Webb AJ, Lundberg JO, Weitzberg E. Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases. J Intern Med. 2016;279(4):315–36.PubMedCrossRef
3.
go back to reference McNally B, Griffin JL, Roberts LD. Dietary inorganic nitrate: from villain to hero in metabolic disease? Mol Nutr Food Res. 2016;60(1):67–78.PubMedCrossRef McNally B, Griffin JL, Roberts LD. Dietary inorganic nitrate: from villain to hero in metabolic disease? Mol Nutr Food Res. 2016;60(1):67–78.PubMedCrossRef
4.
go back to reference Lundberg JO, Gladwin MT, Ahluwalia A, Benjamin N, Bryan NS, Butler A, et al. Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol. 2009;5(12):865–9.PubMedPubMedCentralCrossRef Lundberg JO, Gladwin MT, Ahluwalia A, Benjamin N, Bryan NS, Butler A, et al. Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol. 2009;5(12):865–9.PubMedPubMedCentralCrossRef
5.
6.
go back to reference El-Wakf AM, Hassan HA, Mahmoud AZ, Habza MN. Fenugreek potent activity against nitrate-induced diabetes in young and adult male rats. Cytotechnology. 2015;67(3):437–47.PubMedCrossRef El-Wakf AM, Hassan HA, Mahmoud AZ, Habza MN. Fenugreek potent activity against nitrate-induced diabetes in young and adult male rats. Cytotechnology. 2015;67(3):437–47.PubMedCrossRef
7.
go back to reference Novelli M, Pocai A, Lajoix AD, Beffy P, Bezzi D, Marchetti P, et al. Alteration of beta-cell constitutive NO synthase activity is involved in the abnormal insulin response to arginine in a new rat model of type 2 diabetes. Mol Cell Endocrinol. 2004;219(1–2):77–82.PubMedCrossRef Novelli M, Pocai A, Lajoix AD, Beffy P, Bezzi D, Marchetti P, et al. Alteration of beta-cell constitutive NO synthase activity is involved in the abnormal insulin response to arginine in a new rat model of type 2 diabetes. Mol Cell Endocrinol. 2004;219(1–2):77–82.PubMedCrossRef
8.
go back to reference Lajoix AD, Reggio H, Chardes T, Peraldi-Roux S, Tribillac F, Roye M, et al. A neuronal isoform of nitric oxide synthase expressed in pancreatic beta-cells controls insulin secretion. Diabetes. 2001;50(6):1311–23.PubMedCrossRef Lajoix AD, Reggio H, Chardes T, Peraldi-Roux S, Tribillac F, Roye M, et al. A neuronal isoform of nitric oxide synthase expressed in pancreatic beta-cells controls insulin secretion. Diabetes. 2001;50(6):1311–23.PubMedCrossRef
9.
go back to reference Broniowska KA, Oleson BJ, Corbett JA. Chapter Twelve - β-Cell Responses to Nitric Oxide. In: Litwack G, editor. Vitamins & Hormones. Cambridge: Academic Press; 2014. p. 299–322. Broniowska KA, Oleson BJ, Corbett JA. Chapter Twelve - β-Cell Responses to Nitric Oxide. In: Litwack G, editor. Vitamins & Hormones. Cambridge: Academic Press; 2014. p. 299–322.
10.
go back to reference Smukler SR, Tang L, Wheeler MB, Salapatek AM. Exogenous nitric oxide and endogenous glucose-stimulated beta-cell nitric oxide augment insulin release. Diabetes. 2002;51(12):3450–60.PubMedCrossRef Smukler SR, Tang L, Wheeler MB, Salapatek AM. Exogenous nitric oxide and endogenous glucose-stimulated beta-cell nitric oxide augment insulin release. Diabetes. 2002;51(12):3450–60.PubMedCrossRef
11.
go back to reference Henningsson R, Salehi A, Lundquist I. Role of nitric oxide synthase isoforms in glucose-stimulated insulin release. Am J Physiol Cell Physiol. 2002;283(1):C296–304.PubMedCrossRef Henningsson R, Salehi A, Lundquist I. Role of nitric oxide synthase isoforms in glucose-stimulated insulin release. Am J Physiol Cell Physiol. 2002;283(1):C296–304.PubMedCrossRef
12.
go back to reference Jones PM, Persaud SJ, Bjaaland T, Pearson JD, Howell SL. Nitric oxide is not involved in the initiation of insulin secretion from rat islets of Langerhans. Diabetologia. 1992;35(11):1020–7.PubMedCrossRef Jones PM, Persaud SJ, Bjaaland T, Pearson JD, Howell SL. Nitric oxide is not involved in the initiation of insulin secretion from rat islets of Langerhans. Diabetologia. 1992;35(11):1020–7.PubMedCrossRef
13.
go back to reference Salehi A, Meidute Abaraviciene S, Jimenez-Feltstrom J, Ostenson CG, Efendic S, Lundquist I. Excessive islet NO generation in type 2 diabetic GK rats coincides with abnormal hormone secretion and is counteracted by GLP-1. PLoS One. 2008;3(5):e2165.PubMedPubMedCentralCrossRef Salehi A, Meidute Abaraviciene S, Jimenez-Feltstrom J, Ostenson CG, Efendic S, Lundquist I. Excessive islet NO generation in type 2 diabetic GK rats coincides with abnormal hormone secretion and is counteracted by GLP-1. PLoS One. 2008;3(5):e2165.PubMedPubMedCentralCrossRef
14.
go back to reference Ghasemi A, Jeddi S. Anti-obesity and anti-diabetic effects of nitrate and nitrite. Nitric Oxide. 2017;70:9–24.PubMedCrossRef Ghasemi A, Jeddi S. Anti-obesity and anti-diabetic effects of nitrate and nitrite. Nitric Oxide. 2017;70:9–24.PubMedCrossRef
15.
go back to reference Pitocco D, Tesauro M, Alessandro R, Ghirlanda G, Cardillo C. Oxidative stress in diabetes: implications for vascular and other complications. Int J Mol Sci. 2013;14(11):21525–50.PubMedPubMedCentralCrossRef Pitocco D, Tesauro M, Alessandro R, Ghirlanda G, Cardillo C. Oxidative stress in diabetes: implications for vascular and other complications. Int J Mol Sci. 2013;14(11):21525–50.PubMedPubMedCentralCrossRef
16.
go back to reference Wang J, Wang H. Oxidative stress in pancreatic Beta cell regeneration. Oxidative Med Cell Longev. 2017;2017:1930261–9. Wang J, Wang H. Oxidative stress in pancreatic Beta cell regeneration. Oxidative Med Cell Longev. 2017;2017:1930261–9.
17.
go back to reference Carlström M, Larsen FJ, Nyström T, Hezel M, Borniquel S, Weitzberg E, et al. Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice. Proc Natl Acad Sci U S A. 2010;107(41):17716–20.PubMedPubMedCentralCrossRef Carlström M, Larsen FJ, Nyström T, Hezel M, Borniquel S, Weitzberg E, et al. Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice. Proc Natl Acad Sci U S A. 2010;107(41):17716–20.PubMedPubMedCentralCrossRef
18.
go back to reference Gadek-Michalska A, Bugajski J. Role of nitric oxide in the nicotine-induced pituitary-adrenocortical response. J Physiol Pharmacol. 2004;55(2):443–55.PubMed Gadek-Michalska A, Bugajski J. Role of nitric oxide in the nicotine-induced pituitary-adrenocortical response. J Physiol Pharmacol. 2004;55(2):443–55.PubMed
19.
go back to reference Farrokhfall K, Khoshbaten A, Zahediasl S, Mehrani H, Karbalaei N. Improved islet function is associated with anti-inflammatory, antioxidant and hypoglycemic potential of cinnamaldehyde on metabolic syndrome induced by high tail fat in rats. J Funct Foods. 2014;10:397–406.CrossRef Farrokhfall K, Khoshbaten A, Zahediasl S, Mehrani H, Karbalaei N. Improved islet function is associated with anti-inflammatory, antioxidant and hypoglycemic potential of cinnamaldehyde on metabolic syndrome induced by high tail fat in rats. J Funct Foods. 2014;10:397–406.CrossRef
20.
go back to reference Safayee S, Karbalaei N, Noorafshan A, Nadimi E. Induction of oxidative stress, suppression of glucose-induced insulin release, ATP production, glucokinase activity, and histomorphometric changes in pancreatic islets of hypothyroid rat. Eur J Pharmacol. 2016;791:147–56.PubMedCrossRef Safayee S, Karbalaei N, Noorafshan A, Nadimi E. Induction of oxidative stress, suppression of glucose-induced insulin release, ATP production, glucokinase activity, and histomorphometric changes in pancreatic islets of hypothyroid rat. Eur J Pharmacol. 2016;791:147–56.PubMedCrossRef
21.
go back to reference Karbalaei N, Noorafshan A, Hoshmandi E. Impaired glucose-stimulated insulin secretion and reduced beta-cell mass in pancreatic islets of hyperthyroid rats. Exp Physiol. 2016;101(8):1114–27.PubMedCrossRef Karbalaei N, Noorafshan A, Hoshmandi E. Impaired glucose-stimulated insulin secretion and reduced beta-cell mass in pancreatic islets of hyperthyroid rats. Exp Physiol. 2016;101(8):1114–27.PubMedCrossRef
22.
go back to reference Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72(1):248–54.CrossRefPubMed Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72(1):248–54.CrossRefPubMed
23.
go back to reference Zhu W, Chen M, Shou Q, Li Y, Hu F. Biological activities of Chinese Propolis and Brazilian Propolis on Streptozotocin-induced type 1 diabetes mellitus in rats. Evid Based Complement Alternat Med. 2011;2011:1–8. Zhu W, Chen M, Shou Q, Li Y, Hu F. Biological activities of Chinese Propolis and Brazilian Propolis on Streptozotocin-induced type 1 diabetes mellitus in rats. Evid Based Complement Alternat Med. 2011;2011:1–8.
24.
go back to reference Broulik PD, Haluzik M, Skrha J. The influence of nitric oxide synthase inhibitor L-NAME on bones of male rats with streptozotocin-induced diabetes. Physiol Res. 2003;52(6):729–34.PubMed Broulik PD, Haluzik M, Skrha J. The influence of nitric oxide synthase inhibitor L-NAME on bones of male rats with streptozotocin-induced diabetes. Physiol Res. 2003;52(6):729–34.PubMed
25.
go back to reference Ogur R, Coskun O, Korkmaz A, Oter S, Yaren H, Hasde M. High nitrate intake impairs liver functions and morphology in rats; protective effects of alpha-tocopherol. Environ Toxicol Pharmacol. 2005;20(1):161–6.PubMedCrossRef Ogur R, Coskun O, Korkmaz A, Oter S, Yaren H, Hasde M. High nitrate intake impairs liver functions and morphology in rats; protective effects of alpha-tocopherol. Environ Toxicol Pharmacol. 2005;20(1):161–6.PubMedCrossRef
26.
go back to reference National TP. Toxicology and carcinogenesis studies of sodium nitrite (CAS NO. 7632-00-0) in F344/N rats and B6C3F1 mice (drinking water studies). Natl Toxicol Program Tech Rep Ser. 2001;495:7–273. National TP. Toxicology and carcinogenesis studies of sodium nitrite (CAS NO. 7632-00-0) in F344/N rats and B6C3F1 mice (drinking water studies). Natl Toxicol Program Tech Rep Ser. 2001;495:7–273.
27.
go back to reference Til HP, Kuper CF, Falke HE. Nitrite-induced adrenal effects in rats and the consequences for the no-observed-effect level. Food Chem Toxicol. 1997;35(3–4):349–55.PubMedCrossRef Til HP, Kuper CF, Falke HE. Nitrite-induced adrenal effects in rats and the consequences for the no-observed-effect level. Food Chem Toxicol. 1997;35(3–4):349–55.PubMedCrossRef
28.
go back to reference Khalifi S, Rahimipour A, Jeddi S, Ghanbari M, Kazerouni F, Ghasemi A. Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia. Nitric Oxide. 2015;44:24–30.PubMedCrossRef Khalifi S, Rahimipour A, Jeddi S, Ghanbari M, Kazerouni F, Ghasemi A. Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia. Nitric Oxide. 2015;44:24–30.PubMedCrossRef
29.
go back to reference Akasha M, A. K, A. AS. Effect of Nitrate on the Body Weight, Food and Water Consumption and Thyroid Hormone in Hybrid Female Rabbits. J Vet Adv. 2015;5(5):912–8.CrossRef Akasha M, A. K, A. AS. Effect of Nitrate on the Body Weight, Food and Water Consumption and Thyroid Hormone in Hybrid Female Rabbits. J Vet Adv. 2015;5(5):912–8.CrossRef
30.
go back to reference Kato Y, Miura Y, Yamamoto N, Ozaki N, Oiso Y. Suppressive effects of a selective inducible nitric oxide synthase (iNOS) inhibitor on pancreatic beta-cell dysfunction. Diabetologia. 2003;46(9):1228–33.PubMedCrossRef Kato Y, Miura Y, Yamamoto N, Ozaki N, Oiso Y. Suppressive effects of a selective inducible nitric oxide synthase (iNOS) inhibitor on pancreatic beta-cell dysfunction. Diabetologia. 2003;46(9):1228–33.PubMedCrossRef
31.
go back to reference Muhammed SJ, Lundquist I, Salehi A. Pancreatic beta-cell dysfunction, expression of iNOS and the effect of phosphodiesterase inhibitors in human pancreatic islets of type 2 diabetes. Diabetes Obes Metab. 2012;14(11):1010–9.PubMedCrossRef Muhammed SJ, Lundquist I, Salehi A. Pancreatic beta-cell dysfunction, expression of iNOS and the effect of phosphodiesterase inhibitors in human pancreatic islets of type 2 diabetes. Diabetes Obes Metab. 2012;14(11):1010–9.PubMedCrossRef
32.
go back to reference Bedoya FJ, Salguero-Aranda C, Cahuana GM, Tapia-Limonchi R, Soria B, Tejedo JR. Regulation of pancreatic beta-cell survival by nitric oxide: clinical relevance. Islets. 2012;4(2):108–18.PubMedCrossRef Bedoya FJ, Salguero-Aranda C, Cahuana GM, Tapia-Limonchi R, Soria B, Tejedo JR. Regulation of pancreatic beta-cell survival by nitric oxide: clinical relevance. Islets. 2012;4(2):108–18.PubMedCrossRef
33.
go back to reference McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JA. Cytokines and nitric oxide in islet inflammation and diabetes. Proc Soc Exp Biol Med. 1996;211(1):24–32.PubMedCrossRef McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JA. Cytokines and nitric oxide in islet inflammation and diabetes. Proc Soc Exp Biol Med. 1996;211(1):24–32.PubMedCrossRef
34.
go back to reference Yang T, Peleli M, Zollbrecht C, Giulietti A, Terrando N, Lundberg JO, et al. Inorganic nitrite attenuates NADPH oxidase-derived superoxide generation in activated macrophages via a nitric oxide-dependent mechanism. Free Radic Biol Med. 2015;83:159–66.PubMedCrossRef Yang T, Peleli M, Zollbrecht C, Giulietti A, Terrando N, Lundberg JO, et al. Inorganic nitrite attenuates NADPH oxidase-derived superoxide generation in activated macrophages via a nitric oxide-dependent mechanism. Free Radic Biol Med. 2015;83:159–66.PubMedCrossRef
35.
go back to reference Carlström M, Liu M, Yang T, Zollbrecht C, Huang L, Peleli M, et al. Cross-talk between nitrate-nitrite-NO and NO synthase pathways in control of vascular NO homeostasis. Antioxid Redox Signal. 2015;23(4):295–306.PubMedPubMedCentralCrossRef Carlström M, Liu M, Yang T, Zollbrecht C, Huang L, Peleli M, et al. Cross-talk between nitrate-nitrite-NO and NO synthase pathways in control of vascular NO homeostasis. Antioxid Redox Signal. 2015;23(4):295–306.PubMedPubMedCentralCrossRef
36.
go back to reference Jiang H, Torregrossa AC, Potts A, Pierini D, Aranke M, Garg HK. Dietary nitrite improves insulin signaling through GLUT4 translocation. Free Radic Biol Med. 2014;67:51–7.PubMedCrossRef Jiang H, Torregrossa AC, Potts A, Pierini D, Aranke M, Garg HK. Dietary nitrite improves insulin signaling through GLUT4 translocation. Free Radic Biol Med. 2014;67:51–7.PubMedCrossRef
37.
go back to reference Ohtake K, Nakano G, Ehara N, Sonoda K, Ito J, Uchida H. Dietary nitrite supplementation improves insulin resistance in type 2 diabetic KKA(y) mice. Nitric Oxide. 2015;44:31–8.PubMedCrossRef Ohtake K, Nakano G, Ehara N, Sonoda K, Ito J, Uchida H. Dietary nitrite supplementation improves insulin resistance in type 2 diabetic KKA(y) mice. Nitric Oxide. 2015;44:31–8.PubMedCrossRef
38.
go back to reference Nino Fong R, Fatehi-Hassanabad Z, Lee SC, Lu H, Wheeler MB, Chan CB. Uncoupling protein-2 increases nitric oxide production and TNFAIP3 pathway activation in pancreatic islets. J Mol Endocrinol. 2011;46(3):193–204.PubMedPubMedCentralCrossRef Nino Fong R, Fatehi-Hassanabad Z, Lee SC, Lu H, Wheeler MB, Chan CB. Uncoupling protein-2 increases nitric oxide production and TNFAIP3 pathway activation in pancreatic islets. J Mol Endocrinol. 2011;46(3):193–204.PubMedPubMedCentralCrossRef
39.
go back to reference Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes. 2005;54(Suppl 2):S97–S107.PubMedCrossRef Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes. 2005;54(Suppl 2):S97–S107.PubMedCrossRef
40.
go back to reference Qader SS, Ekelund M, Andersson R, Obermuller S, Salehi A. Acute pancreatitis, expression of inducible nitric oxide synthase and defective insulin secretion. Cell Tissue Res. 2003;313(3):271–9.PubMedCrossRef Qader SS, Ekelund M, Andersson R, Obermuller S, Salehi A. Acute pancreatitis, expression of inducible nitric oxide synthase and defective insulin secretion. Cell Tissue Res. 2003;313(3):271–9.PubMedCrossRef
41.
go back to reference Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med. 2011;50(5):567–75.CrossRefPubMed Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med. 2011;50(5):567–75.CrossRefPubMed
42.
go back to reference Pacher P, Obrosova IG, Mabley JG, Szabo C. Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications. Emerging new therapeutical strategies. Curr Med Chem. 2005;12(3):267–75.PubMedPubMedCentralCrossRef Pacher P, Obrosova IG, Mabley JG, Szabo C. Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications. Emerging new therapeutical strategies. Curr Med Chem. 2005;12(3):267–75.PubMedPubMedCentralCrossRef
43.
go back to reference Maritim AC, Sanders RA, Watkins JB 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol. 2003;17(1):24–38.PubMedCrossRef Maritim AC, Sanders RA, Watkins JB 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol. 2003;17(1):24–38.PubMedCrossRef
44.
go back to reference Tiedge M, Lortz S, Munday R, Lenzen S. Protection against the co-operative toxicity of nitric oxide and oxygen free radicals by overexpression of antioxidant enzymes in bioengineered insulin-producing RINm5F cells. Diabetologia. 1999;42(7):849–55.PubMedCrossRef Tiedge M, Lortz S, Munday R, Lenzen S. Protection against the co-operative toxicity of nitric oxide and oxygen free radicals by overexpression of antioxidant enzymes in bioengineered insulin-producing RINm5F cells. Diabetologia. 1999;42(7):849–55.PubMedCrossRef
45.
46.
go back to reference Seven A, Guzel S, Seymen O, Civelek S, Bolayirli M, Yigit G, et al. Nitric oxide synthase inhibition by L-NAME in streptozotocin induced diabetic rats: impacts on oxidative stress. Tohoku J Exp Med. 2003;199(4):205–10.PubMedCrossRef Seven A, Guzel S, Seymen O, Civelek S, Bolayirli M, Yigit G, et al. Nitric oxide synthase inhibition by L-NAME in streptozotocin induced diabetic rats: impacts on oxidative stress. Tohoku J Exp Med. 2003;199(4):205–10.PubMedCrossRef
47.
go back to reference Sheweita SA, Mashaly S, Newairy AA, Abdou HM, Eweda SM. Changes in oxidative stress and antioxidant enzyme activities in Streptozotocin-induced diabetes mellitus in rats: role of Alhagi maurorum extracts. Oxidative Med Cell Longev. 2016;2016:5264064. Sheweita SA, Mashaly S, Newairy AA, Abdou HM, Eweda SM. Changes in oxidative stress and antioxidant enzyme activities in Streptozotocin-induced diabetes mellitus in rats: role of Alhagi maurorum extracts. Oxidative Med Cell Longev. 2016;2016:5264064.
48.
go back to reference Carlstrom M, Persson AE, Larsson E, Hezel M, Scheffer PG, Teerlink T. Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension. Cardiovasc Res. 2011;89:574–85.PubMedCrossRef Carlstrom M, Persson AE, Larsson E, Hezel M, Scheffer PG, Teerlink T. Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension. Cardiovasc Res. 2011;89:574–85.PubMedCrossRef
Metadata
Title
Improving effect of combined inorganic nitrate and nitric oxide synthase inhibitor on pancreatic oxidative stress and impaired insulin secretion in streptozotocin induced-diabetic rats
Authors
Zahra Shabgard Shahraki
Narges Karbalaei
Marzieh Nemati
Publication date
01-06-2020
Publisher
Springer International Publishing
Published in
Journal of Diabetes & Metabolic Disorders / Issue 1/2020
Electronic ISSN: 2251-6581
DOI
https://doi.org/10.1007/s40200-020-00516-1

Other articles of this Issue 1/2020

Journal of Diabetes & Metabolic Disorders 1/2020 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine