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

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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.

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Acknowledgements

The present work was financially supported by Shiraz University of Medical Sciences, Shiraz, Iran (grant no. 12977); it is a part of Ms. Thesis by Zahra Shabgard Shahraki. The funders had no role in study design, data collection and analysis and preparation of the manuscript.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Zahra Shabgard Shahraki, Narges Karbalaei & Marzieh Nemati

  2. Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Narges Karbalaei

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  1. Zahra Shabgard Shahraki
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All authors have contributed to the conception and design of the research. Z.S.S, M.N. performed the experiments/analysis. N.K. conceived the study. All authors have participated in drafting the article or revising it and approved the final version.

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Correspondence to Narges Karbalaei.

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Shahraki, Z.S., Karbalaei, N. & Nemati, M. Improving effect of combined inorganic nitrate and nitric oxide synthase inhibitor on pancreatic oxidative stress and impaired insulin secretion in streptozotocin induced-diabetic rats. J Diabetes Metab Disord 19, 353–362 (2020). https://doi.org/10.1007/s40200-020-00516-1

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