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Comparative Analysis of the Effects of Insulin and Metformin on the Ulcerogenic Action of Indomethacin in Rats with Streptozotocin-Induced Diabetes

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Abstract

One consequence of diabetes is gastropathy, manifested by an increase in gastric ulcer formation. Insulin is the primary medication used to treat type 1 diabetes. Metformin, used for type 2 diabetes, is also considered for treating type 1 diabetes. The aim of the study is to compare the effects of insulin and metformin on the ulcerogenic action of indomethacin (IM) in rats with streptozotocin-induced diabetes (type 1 diabetes) as well as in non-diabetic rats. Streptozotocin (STR, 60 mg/kg, i.p.) was administered once 2 weeks before IM administration (35 mg/kg, s.c.) to Sprague-Dawley male rats. The development of diabetes was assessed based on blood glucose levels and changes in body weight. Insulin (2 IU/kg, i.p.) or metformin (100 mg/kg, per os) was administered daily, starting from the 8th day after STR administration, for 7 days. Rats were fasted for 20 hours before IM administration. Four hours after IM administration, rats were decapitated, blood was collected to test corticosterone and glucose levels, and stomachs were extracted to assess the area of IM-induced erosions. During the first week after STR administration, characteristic signs of type 1 diabetes developed: an increase in blood glucose levels and slowed body weight gain. Signs of chronic stress appeared after 2 weeks. The development of STR-induced diabetes led to a marked exacerbation of the ulcerogenic action of IM, as evidenced by the increased average area of IM-induced erosions. The administration of both insulin and metformin prevented the pro-ulcerogenic action of type 1 diabetes under IM-induced ulcer formation conditions. For insulin, but not metformin, a gastroprotective effect was also observed in non-diabetic rats. The results obtained indicate the equal effectiveness of insulin and metformin in correcting the pro-ulcerogenic action of STR-induced diabetes in rats: both drugs prevented it. However, under our experimental conditions, in non-diabetic rats a gastroprotective effect was observed only for insulin.

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ACKNOWLEDGMENTS

We express our gratitude to the staff of the Laboratory of Experimental Endocrinology of the Pavlov Institute of Physiology of the Russian Academy of Sciences: Kolbasova T.I., Afanasyeva L.A. for assistance in conducting experiments.

Funding

The study was supported by a grant of the WCRC (agreement no. 075-15-2022-303 dated April 21, 2022) Pavlov Center “Integrative physiology—medicine, high-tech healthcare and stress tolerance technologies”.

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Authors and Affiliations

  1. Pavlov Institute of Physiology, St. Petersburg, Russia

    N. I. Yarushkina, T. T. Podvigina, O. P. Komkova, O. Yu. Morozova, P. V. Punina & L. P. Filaretova

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  1. N. I. Yarushkina
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  2. T. T. Podvigina
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  3. O. P. Komkova
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  4. O. Yu. Morozova
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Contributions

The idea of the work and planning of the experiment (L.P.F., T.T.P.), conducting the experiment (O.P.K., T.T.P., O.Yu.M, P.V.P.), data processing (N.I.Ya., O.P.K.), writing and editing the manuscript (L.P.F., N.I.Ya., T.T.P.).

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Correspondence to N. I. Yarushkina.

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ETHICS APPROVAL AND CONSENT TO PARTICIPATE

All experiments were conducted in compliance with ethical standards approved by the legal acts of the Russian Federation, the principles of the Basel Declaration and the recommendations of the Commission on Animal Housing and Use of the Pavlov Institute of Physiology of the Russian Academy of Sciences (Protocol no. 01/24 of January 24, 2022).

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The authors of this work declare that they have no conflicts of interest.

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Translated by A. Dyomina

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Yarushkina, N.I., Podvigina, T.T., Komkova, O.P. et al. Comparative Analysis of the Effects of Insulin and Metformin on the Ulcerogenic Action of Indomethacin in Rats with Streptozotocin-Induced Diabetes. J Evol Biochem Phys 59, 2399–2412 (2023). https://doi.org/10.1134/S0022093023060406

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