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Model of the formation of streptozotocin-induced diabetes in Wiesenau pigs with assessment of its effectiveness and stability

https://doi.org/10.14341/DM13168

Abstract

BACKGROUND: Research aimed at creating and validating models of diabetes plays an important role in the development of new treatments for this disease. Large animal models may bridge the gap between basic research and clinical trials of new technologies for the treatment of insulin deficiency. At the moment, the most popular model is streptozotocin-induced diabetes. However, different species and breeds of animals respond differently to streptozotocin. Thus, although models already exist in different breeds of pigs, verification of the Wiesenau pig model of streptozotocin-induced diabetes is an important task, since this breed has not yet been used, and it is also one of the most accessible breeds of laboratory pigs in the world. Russia.

AIM: To reproduce the model of streptozotocin-induced diabetes in Wiesenau pigs with correction of hyperglycemia by insulin therapy and evaluate its stability and compliance with the experimental model of type 1 diabetes.

MATERIALS AND METHODS: The study was performed on 6 Wiesenau pigs. Diabetes was induced by intravenous administration of streptozotocin (150 mg/kg). Blood glucose concentration was determined with a glucometer and a continuous glucose monitoring system was used. The content of insulin in the blood was determined by enzyme-linked immunosorbent assay (Cloud-clone corp). The success of diabetes induction was confirmed by a glucose tolerance test. Seven days after the injection of STZ, insulin therapy was initiated and continued for three months. Insulin therapy was carried out for three months. 3 months after induction, a histological and immunohistochemical study of the condition of the pancreatic islets was carried out.

RESULTS: A study in Wiesenau pigs showed that a dose of 150 mg/kg streptozotocin was safe and effective in inducing diabetes in 67% of cases. An optimal individual insulin therapy protocol was selected, which successfully reduces blood glucose levels to normal values. This model of streptozotocin-induced diabetes in Wiesenau pigs is stable for 90 days and can be used to study new antidiabetic agents.

CONCLUSION: A model of STZ-induced diabetes has been established in Wiesenau pigs. The stability of the model has been confirmed under conditions of glucose toxicity alleviation through insulin therapy.

About the Authors

P. S. Ermakova
Privolzhsky Research Medical University
Russian Federation

Polina S. Ermakova

10/1 Minin and Pozharsky Square, 603005, Nizhny Novgorod



L. A. Lugovaya
Privolzhsky Research Medical University
Russian Federation

Liya A. Lugovaya, PhD

10/1 Minin and Pozharsky Square, 603005, Nizhny Novgorod



E. A. Vasilchikova
Privolzhsky Research Medical University; N.I. Lobachevsky National Research Nizhny Novgorod State University
Russian Federation

Ekaterina A. Vasilchikova

10/1 Minin and Pozharsky Square, 603005, Nizhny Novgorod



A. Y. Bogomolova
Privolzhsky Research Medical University
Russian Federation

Alexandra Y. Bogomolova

10/1 Minin and Pozharsky Square, 603005, Nizhny Novgorod



Y. M. Tselousova
Privolzhsky Research Medical University
Russian Federation

Yulia M. Tselousova

10/1 Minin and Pozharsky Square, 603005, Nizhny Novgorod



N. U. Naraliev
Privolzhsky Research Medical University
Russian Federation

Nasib U. Naraliev

10/1 Minin and Pozharsky Square, 603005, Nizhny Novgorod



D. M. Kuchin
Privolzhsky Research Medical University; N.A. Semashko Nizhny Novgorod Regional Clinical Hospital
Russian Federation

Denis M. Kuchin, PhD

10/1 Minin and Pozharsky Square, 603005, Nizhny Novgorod



E. V. Zagainova
Privolzhsky Research Medical University; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine
Russian Federation

Elena V. Zagainova, MD, PhD, Professor

10/1 Minin and Pozharsky Square, 603005, Nizhny Novgorod



V. E. Zagainov
Privolzhsky Research Medical University; Nizhny Novgorod Regional Oncology Dispensary
Russian Federation

Vladimir E. Zagainov, MD, PhD, Professor

10/1 Minin and Pozharsky Square, 603005, Nizhny Novgorod



A. V. Kashina
Privolzhsky Research Medical University
Russian Federation

Aleksandra V. Kashina, PhD

10/1 Minin and Pozharsky Square, 603005, Nizhny Novgorod



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Supplementary files

1. Рисунок 1. Схема крепления датчика Freestyle Libre для мониторинга глюкозы в крови свиней породы Wiesenau.
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2. Рисунок 2. Динамика уровня глюкозы в крови в первые 24 часа после введения стрептозотоцина свиньям (медиана и интерквартильный размах).
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3. Рисунок 3. Изменение уровней глюкозы и инсулина в крови у свиней со стрептозотоцин-индуцированным диабетом в ответ на введение глюкозы по сравнению со здоровым животным (норма) (медиана и интерквартильный размах). Все данные статистически значимо отличаются по отношению в контролю (норма) (p<0,005).
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4. Рисунок 4. Динамика уровня глюкозы в крови свиней в ходе эксперимента (медиана и интерквартильный размах).
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5. Рисунок 5. Динамика уровня глюкозы в крови свиней, полученная с использованием системы непрерывного мониторинга глюкозы Freestyle Libre.
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6. Рисунок 6. Уровень глюкозы в крови и количество β-клеток в островках Лангерганса свиней через три месяца после введения стрептозотоцина по сравнению со здоровым животным (норма) (медиана и интерквартильный размах). Все данные статистически значимо отличаются по отношению к контролю (норма) (p<0,005).
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7. Рисунок 7. Гистологические изображения ткани поджелудочной железы свиньи (окрашивание гематоксилином и эозином. Об. х40).
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8. Рисунок 8. Изображения ткани поджелудочной железы свиньи (иммуногистохимическое окрашивание. Об. х40).
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Review

For citations:


Ermakova P.S., Lugovaya L.A., Vasilchikova E.A., Bogomolova A.Y., Tselousova Y.M., Naraliev N.U., Kuchin D.M., Zagainova E.V., Zagainov V.E., Kashina A.V. Model of the formation of streptozotocin-induced diabetes in Wiesenau pigs with assessment of its effectiveness and stability. Diabetes mellitus. 2025;28(2):111-123. (In Russ.) https://doi.org/10.14341/DM13168

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ISSN 2072-0351 (Print)
ISSN 2072-0378 (Online)