Age dynamics of strain differences in the morphofunctional state of pancreatic beta- and amylin-producing cells in SHR and Wistar rats

Authors

DOI:

https://doi.org/10.14739/2409-2932.2023.3.286820

Keywords:

pancreatic islets, hypertension, insulin, amylin, Wistar rats, SHR

Abstract

Large-scale epidemiological studies have shown that cardiac pathology and progressive atherosclerosis in patients with diabetes mellitus occurred already at the stage of prediabetes. Obesity and insulin resistance affect cardiometabolic health due to pleiotropic effects of insulin. Despite the vast range of research, some aspects remain hidden links in the overall pathogenesis of metabolic and hemodynamic disorders.

The aim of the work was to study the morphofunctional state of pancreatic islets (PIs), beta- and amylin-producing cells in male rats of Wistar strain (normotensive) and SHR (with spontaneous development of hypertension) in age dynamics.

Materials and methods. The study was carried out using 38 male Wistar rats and SHRs aged 7 and 24 months. Non-invasive blood pressure (BP) detection procedures were done using the BP-2000 Blood Pressure Analysis System. The morphofunctional state of PIs was examined in serial 5-μm thick pancreatic tissue sections. Beta- and amylin-producing cells were detected after histological preprocessing and the use of monoclonal FITC-conjugated antibodies. Image file processing was done via ImageJ software (National Institutes of Health, USA). Levels of glycemia were monitored with a SUPER GLUCOCARD-II glucometer.

Results. SHRs were hyperglycemic both at 7 and at 24 months, 8.41 ± 0.15 mmol/l and 8.90 ± 0.14 mmol/l, respectively, with elevated BP, 155 ± 5 / 80 ± 5 mm Hg and 165 ± 5 / 90 ± 5 mm, respectively. Old SHRs developed PI hypertrophy mainly associated with the increased number and percentage of beta-cells, apparently in response to hyperglycemia. Both in the PIs of adult and old SHRs, the number of amylin-producing cells was lower while the content of amylin was higher than those in the age-matched Wistar rats.

Conclusions. Male SHRs are characterized by a persistent increase in blood pressure and abnormalities of carbohydrate metabolism already at adult age, one of the manifestations of which is hyperglycemia worsening with age. Chronic hyperglycemia in SHRs due to the higher insulin requirement finds its expression in low content of this hormone in the islets at adult age and decreased its content in beta-cells in old animals.

Author Biographies

T. A. Hrekova, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, Associate Professor of the Department of Pathological Physiology with the Course of Normal Physiology

O. V. Melnikova, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, Associate Professor of the Department of Pathological Physiology with Course of Normal Physiology

Ye. V. Kadzharian, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, Associate Professor of the Department of Pathological Physiology with Course of Normal Physiology

References

Louca, P., Menni, C., & Padmanabhan, S. (2020). Genomic Determinants of Hypertension With a Focus on Metabolomics and the Gut Microbiome. American journal of hypertension, 33(6), 473-481. https://doi.org/10.1093/ajh/hpaa022

Barbu, E., Popescu, M. R., Popescu, A. C., & Balanescu, S. M. (2021). Phenotyping the Prediabetic Population-A Closer Look at Intermediate Glucose Status and Cardiovascular Disease. International journal of molecular sciences, 22(13), 6864. https://doi.org/10.3390/ijms22136864

Liang, Y., Wang, M., Wang, C., Liu, Y., Naruse, K., & Takahashi, K. (2021). The Mechanisms of the Development of Atherosclerosis in Prediabetes. International journal of molecular sciences, 22(8), 4108. https://doi.org/10.3390/ijms22084108

Petrie, J. R., Guzik, T. J., & Touyz, R. M. (2018). Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. The Canadian journal of cardiology, 34(5), 575-584. https://doi.org/10.1016/j.cjca.2017.12.005

Belfiore, A., Malaguarnera, R., Vella, V., Lawrence, M. C., Sciacca, L., Frasca, F., Morrione, A., & Vigneri, R. (2017). Insulin Receptor Isoforms in Physiology and Disease: An Updated View. Endocrine reviews, 38(5), 379-431. https://doi.org/10.1210/er.2017-00073

Bhowmick, D. C., Kudaibergenova, Z., Burnett, L., & Jeremic, A. M. (2022). Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas. Molecules, 27(3), 1021. https://doi.org/10.3390/molecules27031021

Hayden, M. R. (2023). Overview and New Insights into the Metabolic Syndrome: Risk Factors and Emerging Variables in the Development of Type 2 Diabetes and Cerebrocardiovascular Disease. Medicina (Kaunas, Lithuania), 59(3), 561. https://doi.org/10.3390/medicina59030561

Liu, M., Li, N., Qu, C., Gao, Y., Wu, L., & Hu, L. G. (2021). Amylin deposition activates HIF1α and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) signaling in failing hearts of non-human primates. Communications biology, 4(1), 188. https://doi.org/10.1038/s42003-021-01676-3

Lerman, L. O., Kurtz, T. W., Touyz, R. M., Ellison, D. H., Chade, A. R., Crowley, S. D., Mattson, D. L., Mullins, J. J., Osborn, J., Eirin, A., Reckelhoff, J. F., Iadecola, C., & Coffman, T. M. (2019). Animal Models of Hypertension: A Scientific Statement From the American Heart Association. Hypertension, 73(6), e87-e120. https://doi.org/10.1161/HYP.0000000000000090

Janssen, J. A. M. J. L. (2021). Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer. International journal of molecular sciences, 22(15), 7797. https://doi.org/10.3390/ijms22157797

Mancusi, C., Izzo, R., di Gioia, G., Losi, M. A., Barbato, E., & Morisco, C. (2020). Insulin Resistance the Hinge Between Hypertension and Type 2 Diabetes. High blood pressure & cardiovascular prevention, 27(6), 515-526. https://doi.org/10.1007/s40292-020-00408-8

Kolesnyk, Yu. M., & Isachenko, M. I. (2020). Markernyi profil remodeliuvannia miokarda pry riznykh etiopatohenetychnykh formakh arterialnoi hipertenzii v eksperymenti [Marker profile of myocardial remodeling in different etiopathogenetic forms of arterial hypertension in the experiment]. Pathologia, 17(2), 136-141. [in Ukrainian]. https://doi.org/10.14739/2310-1237.2020.2.212721

Szpirer, C. (2020). Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes. Journal of biomedical science, 27(1), 84. https://doi.org/10.1186/s12929-020-00673-8

Di Pino, A., & DeFronzo, R. A. (2019). Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents. Endocrine reviews, 40(6), 1447-1467. https://doi.org/10.1210/er.2018-00141

Gómez-Hernández, A., de Las Heras, N., López-Pastor, A. R., García-Gómez, G., Infante-Menéndez, J., González-López, P., González-Illanes, T., Lahera, V., Benito, M., & Escribano, Ó. (2021). Severe Hepatic Insulin Resistance Induces Vascular Dysfunction: Improvement by Liver-Specific Insulin Receptor Isoform A Gene Therapy in a Murine Diabetic Model. Cells, 10(8), 2035. https://doi.org/10.3390/cells10082035

Mizukami, H., & Kudoh, K. (2022). Diversity of pathophysiology in type 2 diabetes shown by islet pathology. Journal of diabetes investigation, 13(1), 6-13. https://doi.org/10.1111/jdi.13679

Sonne, N., Karsdal, M. A., & Henriksen, K. (2021). Mono and dual agonists of the amylin, calcitonin, and CGRP receptors and their potential in metabolic diseases. Molecular metabolism, 46, 101109. https://doi.org/10.1016/j.molmet.2020.101109

Kahn, S. E., Chen, Y. C., Esser, N., Taylor, A. J., van Raalte, D. H., Zraika, S., & Verchere, C. B. (2021). The β Cell in Diabetes: Integrating Biomarkers With Functional Measures. Endocrine reviews, 42(5), 528-583. https://doi.org/10.1210/endrev/bnab021

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Published

2023-11-03

How to Cite

1.
Hrekova TA, Melnikova OV, Kadzharian YV. Age dynamics of strain differences in the morphofunctional state of pancreatic beta- and amylin-producing cells in SHR and Wistar rats. Current issues in pharmacy and medicine: science and practice [Internet]. 2023Nov.3 [cited 2024Oct.30];16(3):244-8. Available from: http://pharmed.zsmu.edu.ua/article/view/286820