Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia
Abstract
Reduction in nitric oxide (NO) production and bioavailability contribute to the pathogenesis of type 2 diabetes. Administration of nitrate has strong NO-like outcomes in both animals and humans. In this study, we examined the effects of dietary nitrate on glucose tolerance and lipid profile in type 2 diabetic rats. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Thirty-two male Wistar rats were divided into 4 groups: controls (C), control+nitrate (CN), diabetes (D), and diabetes+nitrate (DN). For 8 weeks, the CN and DN groups consumed sodium nitrate (100 mg/L in drinking water) while the C and D groups consumed tap water. Serum nitrate+nitrite (NOx), glucose, lipid profile, total antioxidant capacity (TAC), and catalase (CAT) activity were measured before and at the end of the study. Systolic blood pressure (SBP) was measured every 10 days. Intravenous glucose tolerance test (IVGTT) was performed at the end of the study. Serum NOx decreased in diabetic rats and dietary nitrate restored it to normal values. Increases in serum glucose levels was significantly lower in the DN group compared to the D group (24.1% vs. 90.2%; p < 0.05). Nitrate therapy in diabetic rats significantly improved lipid profile, glucose tolerance (AUC: 20264 ± 659 vs. 17923 ± 523; p < 0.05 for D and DN groups respectively) and restored elevated SBP to normal values. Diabetic rats had lower TAC and CAT activity and dietary nitrate restored these to normal status. In conclusion, dietary nitrate prevented increase in SBP and serum glucose, improved glucose tolerance and restored dyslipidemia in an animal model of hyperglycemia.
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Recent studies demonstrate improvements of insulin resistance in humans and animals as a result of dietary nitrate/nitrite enhancing NO availability in plasma and tissues.
“the therapeutic potential of dietary nitrate/nitrite has been supported by recent studies demonstrating the improvements of insulin resistance in humans and animals as a result of its enhancing the NO availability in plasma and tissues [65,66,67,68].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [68]
Cites
The worldwide epidemiology of type 2 diabetes mellitus—present and future perspectives
Chen, L., Magliano, D. J., & Zimmet, P. Z. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.183 · Cited by 2,227 · see citing works
Nowy rok, stare problemy, ale i nowe możliwości
Czupryniak, L. (2014) · Via Medica Journals · Cited by 1,192 · see citing works
Webb, A. J., Patel, N., Loukogeorgakis, S., Okorie, M., Aboud, Z., Misra, S., Rashid, R., Miall, P., Deanfield, J., Benjamin, N., et al. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.103523 · Cited by 1,078 · see citing works
Food sources of nitrates and nitrites: The physiologic context for potential health benefits
Hord, N. G., Tang, Y., & Bryan, N. S. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.27131 · Cited by 1,069 · see citing works
Masiello, P., Broca, C., Gross, R., Roye, M., Manteghetti, M., Hillaire‐Buys, D., Novelli, M., & Ribes, G. (1998) · Diabetes · doi:10.2337/diab.47.2.224 · Cited by 782 · see citing works
Dietary Inorganic Nitrate Improves Mitochondrial Efficiency in Humans
Larsen, F. J., Schiffer, T. A., Borniquel, S., Sahlin, K., Ekblom, B., Lundberg, J. O., & Weitzberg, E. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.004 · Cited by 689 · see citing works
Benjamin, N., O'Driscoll, F., Dougall, H., Duncan, C., Smith, L., Golden, M., & McKenzie, H. (1994) · Nature · doi:10.1038/368502a0 · Cited by 665 · see citing works
Intragastric nitric oxide production in humans: measurements in expelled air.
Lundberg, J. O., Weitzberg, E., Lundberg, J. M., & Alving, K. (1994) · Gut · doi:10.1136/gut.35.11.1543 · Cited by 661 · see citing works
Effects of dietary nitrate on oxygen cost during exercise
Larsen, F. J., Weitzberg, E., Lundberg, J. O., & Ekblom, B. (2007) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01713.x · Cited by 637 · see citing works
Nitrate and nitrite in biology, nutrition and therapeutics
Lundberg, J. O., Gladwin, M. T., Ahluwalia, A., Benjamin, N., Bryan, N. S., Butler, A., Cabrales, P., Fago, A., Feelisch, M., Ford, P. C., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.260 · Cited by 617 · see citing works
Standards of Medical Care for Patients With Diabetes Mellitus
American Diabetes Association (2003) · Diabetes Care · doi:10.2337/diacare.26.2007.s33 · Cited by 610 · see citing works
Effects of Dietary Nitrate on Blood Pressure in Healthy Volunteers
Larsen, F. J., Ekblom, B., Sahlin, K., Lundberg, J. O., & Weitzberg, E. (2006) · New England Journal of Medicine · doi:10.1056/nejmc062800 · Cited by 587 · see citing works
Streptozotocin–nicotinamide-induced diabetes in the rat. Characteristics of the experimental model
Szkudelski, T. (2012) · Experimental Biology and Medicine · doi:10.1258/ebm.2012.011372 · Cited by 438 · see citing works
Carlström, M., Larsen, F. J., Nyström, T., Hezel, M., Borniquel, S., Weitzberg, E., & Lundberg, J. O. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008872107 · Cited by 382 · see citing works
Differences in plasma cholesteryl ester transfer activity in sixteen vertebrate species
Haa, Y. C., & Barter, P. J. (1982) · Comparative Biochemistry and Physiology Part B Comparative Biochemistry · doi:10.1016/0305-0491(82)90252-8 · Cited by 365 · see citing works
Roles of dietary inorganic nitrate in cardiovascular health and disease
Lundberg, J. O., Carlström, M., Larsen, F. J., & Weitzberg, E. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvq325 · Cited by 355 · see citing works
Ceriello, A., Russo, P. D., Amstad, P., & Cerutti, P. (1996) · Diabetes · doi:10.2337/diab.45.4.471 · Cited by 324 · see citing works
Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis
Grattagliano, I., Palmieri, V. O., Portincasa, P., Moschetta, A., & Palasciano, G. (2007) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2007.06.011 · Cited by 293 · see citing works
Streptozotocin-nicotinamide-induced rat model of type 2 diabetes (review)
Ghasemi, A., Khalifi, S., & Jeddi, S. (2014) · Acta Physiologica Hungarica · doi:10.1556/aphysiol.101.2014.4.2 · Cited by 282 · see citing works
Self-citationCarlström, M., Persson, A. E. G., Larsson, E., Hezel, M., Scheffer, P. G., Teerlink, T., Weitzberg, E., & Lundberg, J. O. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvq366 · Cited by 261 · see citing works
Gilchrist, M., Winyard, P. G., Aizawa, K., Anning, C., Shore, A., & Benjamin, N. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.01.024 · Cited by 261 · see citing works
Nitrite in nitric oxide biology: Cause or consequence?
Bryan, N. S. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.05.019 · Cited by 260 · see citing works
Zhang, Z., Naughton, D., Winyard, P. G., Benjamin, N., Blake, D. R., & Symons, M. C. R. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9226 · Cited by 246 · see citing works
Bhatia, S., Shukla, R., Madhu, S. V., Gambhir, J. K., & Prabhu, K. M. (2003) · Clinical Biochemistry · doi:10.1016/s0009-9120(03)00094-8 · Cited by 221 · see citing works
Patel, H., Chen, J., Das, K. C., & Kavdia, M. (2013) · Cardiovascular Diabetology · doi:10.1186/1475-2840-12-142 · Cited by 179 · see citing works
Afshari, A. T., Shirpoor, A., Farshid, A.-A., Saadatian, R., Rasmi, Y., Saboory, E., Ilkhanizadeh, B., & Allameh, A. (2006) · Food Chemistry · doi:10.1016/j.foodchem.2006.01.013 · Cited by 171 · see citing works
Stokes, K. Y., Dugas, T. R., Tang, Y., Garg, H., Guidry, E., & Bryan, N. S. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01291.2008 · Cited by 171 · see citing works
Sodium nitrite: The “cure” for nitric oxide insufficiency
Parthasarathy, D. K., & Bryan, N. S. (2012) · Meat Science · doi:10.1016/j.meatsci.2012.03.001 · Cited by 157 · see citing works
NO generation from inorganic nitrate and nitrite: Role in physiology, nutrition and therapeutics
Lundberg, J. O., & Weitzberg, E. (2009) · Archives of Pharmacal Research · doi:10.1007/s12272-009-1803-z · Cited by 153 · see citing works
Animal models of type 2 diabetes with reduced pancreatic β-cell mass
Masiello, P. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.09.007 · Cited by 148 · see citing works
Bulhak, A., Jung, C., Östenson, C., Lundberg, J. O., Sjöquist, P.-O. B., & Pernow, J. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00394.2008 · Cited by 116 · see citing works
Dietary nitrite improves insulin signaling through GLUT4 translocation
Jiang, H., Torregrossa, A. C., Potts, A., Pierini, D., Aranke, M., Garg, H. K., & Bryan, N. S. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.10.809 · Cited by 105 · see citing works
L’Abbate, A., Neglia, D., Vecoli, C., Novelli, M., Ottaviano, V., Baldi, S., Barsacchi, R., Paolicchi, A., Masiello, P., Drummond, G. S., et al. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00826.2007 · Cited by 95 · see citing works
Inorganic nitrite stimulates pancreatic islet blood flow and insulin secretion
Nyström, T., Ortsäter, H., Huang, Z., Zhang, F., Larsen, F. J., Weitzberg, E., Lundberg, J. O., & Sjöholm, Å. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.06.031 · Cited by 94 · see citing works
Watcho, P., Gildas, A. J. H., Mbiakop, U. C., Wankeu‐Nya, M., Benoit, N. T., & Kamanyi, A. (2012) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-12-264 · Cited by 71 · see citing works
Impact of nitrate intake in drinking water on the thyroid gland activity in male rat
Zaki, A., Chaoui, A. A., Talibi, A., Derouiche, A. F., Aboussaouira, T., Fellat-Zarrouck, K., Chait, A., & Himmi, T. (2003) · Toxicology Letters · doi:10.1016/j.toxlet.2003.10.010 · Cited by 62 · see citing works
(2001) · PubMed · Cited by 49 · see citing works
Felice, F., Lucchesi, D., Stefano, R. D., Barsotti, M., Storti, E., Penno, G., Balbarini, A., Prato, S. D., & Pucci, L. (2010) · Microvascular Research · doi:10.1016/j.mvr.2010.05.004 · Cited by 48 · see citing works
Ghasemi, A., & Zahediasl, S. (2012) · PubMed · Cited by 45 · see citing works
Self-citationThe biological role of nitrate and nitrite: The times they are a-changin’
Lundberg, J. O., & Weitzberg, E. (2009) · Nitric Oxide · doi:10.1016/j.niox.2009.11.004 · Cited by 42 · see citing works
Oğur, R., Çoşkun, Ö., Korkmaz, A., et al. (2005) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2004.12.051 · Cited by 38 · see citing works
TOTAL ANTIOXIDANT CAPACITY, SUPEROXIDE DISMUTASE AND GLUTATHION PEROXIDASE IN DIABETIC PATIENTS
Noubar, M. R., Rahimipour, A., & Mirhashemi, S. M. (2003) · Cited by 35 · see citing works
Self-citationEbara, T., Hirano, T., Mamo, J. C. L., et al. (1994) · Metabolism · doi:10.1016/0026-0495(94)90096-5 · Cited by 33 · see citing works
Catalase (antioxidant enzyme) activity in streptozotocin-induced diabetic rats
Qujeq, D., & Rezvani, T. (2019) · International Journal of Diabetes and Metabolism · doi:10.1159/000497630 · Cited by 33 · see citing works
Farahani, H., Ghasemi, A., Roghani, M., & Zahediasl, S. (2010) · Hormone and Metabolic Research · doi:10.1055/s-0030-1262826 · Cited by 29 · see citing works
Self-citationCardiovascular prevention by dietary nitrate and nitrite
Lundberg, J. O. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00246.2009 · Cited by 29 · see citing works
Potential Therapeutic Effects of Nitrate/Nitrite and Type 2 Diabetes Mellitus
Ghasemi, A., & Zahediasl, S. (2013) · Intern J Endocrinol Metab · doi:10.5812/ijem.9103 · Cited by 27 · see citing works
Self-citationKarbalaei, N., Ghasemi, A., Faraji, F., et al. (2012) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365513.2012.743164 · Cited by 26 · see citing works
Self-citationAdipocyte dysfunction in rats with streptozotocin–nicotinamide‐induced diabetes
Szkudelska, K., Nogowski, L., & Szkudelski, T. (2014) · International Journal of Experimental Pathology · doi:10.1111/iep.12073 · Cited by 25 · see citing works
Hypothyroidism in Male Rats of Different Ages Exposed to Nitrate Polluted Drinking Water
El‐Wakf, A. M., Hassan, H. A., Elsaid, F. G., et al. (2008) · Mansoura Journal of Forensic Medicine and Clinical Toxicology · doi:10.21608/mjfmct.2008.54096 · Cited by 25 · see citing works
Nitrite-induced adrenal effects in rats and the consequences for the no-observed-effect level
Til, H. P., Kuper, C. F., & Falke, H. E. (1997) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(97)00122-1 · Cited by 23 · see citing works
Fierabracci, V., Tata, V. D., Pocai, A., et al. (2002) · Endocrine · doi:10.1385/endo:19:2:177 · Cited by 23 · see citing works
Cline, T. R., Hatfield, E. E., & Garrigus, U. S. (1963) · Journal of Animal Science · doi:10.2527/jas1963.224911x · Cited by 17 · see citing works
ON NO—The Continuing Story of Nitric Oxide, Diabetes, and Cardiovascular Disease
Bøtker, H. E., & Møller, N. (2013) · Diabetes · doi:10.2337/db13-0542 · Cited by 15 · see citing works
Dietary nitrate – a slow train coming
Weitzberg, E., & Lundberg, J. O. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.220673 · Cited by 8 · see citing works
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Kapil, V., Khambata, R. S., Jones, D. A., Rathod, K., Primus, C., Massimo, G., Fukuto, J. M., & Ahluwalia, A. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019240 · Cited by 248 · see citing works
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- Authors
- Khalifi, S., Rahimipour, A., Jeddi, S., Ghanbari, M., Kazerouni, F., & Ghasemi, A.
- Affiliations
- Shahid Beheshti University (IR)
- Research Institute for Endocrine Sciences (IR)
- Corresponding author
- Ghasemi, Asghar
- Venue
- Nitric Oxide
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 44
- Pages
- 24-30
- ISSN
- 1089-8603 (ISSN-L)
- OpenAlex
- W2013901475
- Semantic Scholar
- 7340e120547db9d91f475d1bbf8fb0ee1945280a
- Cited by
- 95
- References
- 55
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 13 · 2023: 4 · 2022: 9 · 2021: 9 · 2020: 12 · 2019: 9 · 2018: 10 · 2017: 6 · 2016: 3 · 2015: 6
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nitric Oxide (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences (498)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- dietary nitrate, sodium nitrate, type 2 diabetes, glucose tolerance, lipid profile, dyslipidemia, hyperglycemia, nitric oxide bioavailability, streptozotocin-nicotinamide-induced diabetes, systolic blood pressure, antioxidant capacity, catalase, nitrite/nitrate
- MeSH terms
- Animals, Blood Glucose, Body Weight, Diabetes Mellitus, Experimental, Disease Models, Animal, Hyperglycemia, Lipids, Male, Nitrates, Systole, Rats, Wistar, Rats
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