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Nesfatin-1 ameliorates type-2 diabetes-associated reproductive dysfunction in male mice

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Abstract

Purpose

The present study was aimed to demonstrate the recuperative effect of nesfatin-1 on testicular dysfunction in the high-fat diet (HFD)/streptozotocin (STZ)-induced type-2 diabetes mellitus (T2DM) mice.

Method and results

Three experimental groups were formed: (1) vehicle control (VC), (2) T2DM mice, (3) T2DM + nesf-1. The mice with blood glucose level higher than 300 mg/dL following HFD and a single dose of STZ were used for the experiment. The T2DM mice showed increases in body mass, blood glucose and insulin levels, reductions in spermatogenesis and steroidogenesis, production of antioxidative enzymes, and disturbed lipid profile. These alterations were all ameliorated by administration of nesfatin-1 at 20 μg/Kg BW for 15 days. Nesfatin-1 treatment also increased the production of testosterone (T), improved insulin sensitivity, and effectively ameliorated the testicular aberrations, and increased spermatogenesis and steroidogenesis. In addition, nesfatin-1 treatment upregulated the PCNA and Bcl2 expression and inhibited the caspase-3 and prohibitin expression in T2DM mice. Nesfatin-1 increased insulin receptor (IR) and GLUT8 expressions, and lactate production, the changes that further substantiate the increase of energy influx to the testis.

Conclusion

Altogether, the results suggest the ameliorative effect of nesfatin-1 against T2DM-associated testicular dysfunctions and improved insulin sensitivity along with promoting T production and fertility in T2DM mice.

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Acknowledgements

The authors are highly thankful to the Interdisciplinary School of Life Sciences (ISLS) BHU Varanasi for providing instrumentation facility. AR also acknowledges the Centre of Advanced Study (CAS) Zoology, Banaras Hindu University, for financial assistance in the form of fellowship. AR designed and performed the experiment. AR and AK wrote the manuscript draft. MC and TY corrected and edited the manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    A. Ranjan, M. Choubey & A. Krishna

  2. Division of Integrative Physiology, Kansai Electric Power Medical Research Institute, Kobe, 650-0047, Japan

    T. Yada

  3. Division of System Neuroscience, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan

    T. Yada

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  1. A. Ranjan
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  2. M. Choubey
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Correspondence to A. Krishna.

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The present study was approved by the institutional animal ethical committee of Banaras Hindu University following the relevant guidelines and regulations. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (Institutional Animal Ethics Committee (F.Sc/88/IAEC/2016-17/63)). This article does not contain any studies with human participants performed by any of the authors.

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Ranjan, A., Choubey, M., Yada, T. et al. Nesfatin-1 ameliorates type-2 diabetes-associated reproductive dysfunction in male mice. J Endocrinol Invest 43, 515–528 (2020). https://doi.org/10.1007/s40618-019-01136-0

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