Analysis of the activity of c-kit immunopositive alpha-cells of the pancreas in exogenous infusions and endogenously formed pathology

Authors

DOI:

https://doi.org/10.14739/2409-2932.2023.1.273223

Keywords:

SHR rats, Wistar rat, pancreas, pancreatic islet, endocrinocyte, immunofluorescence, glucagon, с-kit

Abstract

There are a number of factors and agents that change the population of endocrinocytes and their secretory activity depending on various conditions and experimentally formed pathologies. These include the impact of intermittent hypoxic hypoxia; experimentally formed pathology (diabetes); genetically formed pathology (arterial hypertension), direct effect on endocrinocytes of the pancreas with their own pathophysiological mechanism. In this context, it is interesting to analyze the state of the progenitor potential of alpha cells depending on the living conditions of the organism, its effects, and developing pathological conditions in it.

The aim of the work is to determine the activity of the proliferative factor c-kit in alpha cells under exogenous factors – intermittent hypoxic hypoxia and endogenously formed pathology – arterial hypertension and diabetes.

Materials and methods. The study was conducted on the pancreas of SHR and Wistar rats. Glucagon and c-kit in pancreatic islets were determined by the immunofluorescence method. The immunofluorescence reaction was studied with an AxioImager-M2 fluorescence microscope.

Results. Analysis of the c-kit positive alpha-cell index in rats with diabetes showed a 5-fold increase. This was explained by the fact, that the development of hyperglycemia in diabetes mellitus was characterized not only by an increased level of glucose in the blood due to insufficient insulin production but also due to an increase in the number of alpha cells, their active proliferation and possible transdifferentiation from beta cells. The number of c-kit positive alpha cells in SHR rats decreased. This may indicate that these changes were not so related to a violation of the modulation of the transcription factor, but to the participation of neurogenic mechanisms. The decrease in c-kit positive alpha cells in animals with hypoxic hypoxia can be explained by transdifferentiation (remodeling) changes, aimed at suppressing proliferative processes in alpha endocrinocytes.

Conclusions. The increase in the number of c-kit positive alpha cells in rats with diabetes is explained by the fact, that the development of hyperglycemia in diabetes is characterized not only by an increased level of glucose in the blood due to insufficient insulin production but also by an increase in the number of alpha cells, their active proliferation and possible transdifferentiation from beta cells. A decrease in the number of c-kit positive alpha cells in SHR rats may indicate that these changes are not so much related to a violation of the modulation of the transcription factor, but to the participation of neurogenic mechanisms. The decrease in c-kit positive alpha cells in animals with hypoxic hypoxia can be explained by transdifferentiation (remodeling) changes, aimed at suppressing proliferative processes in alpha endocrinocytes.

Author Biography

T. V. Ivanenko, Zaporizhzhia State Medical University, Ukraine

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

References

Jennings, R. E., Berry, A. A., Strutt, J. P., Gerrard, D. T., & Hanley, N. A. (2015). Human pancreas development. Development, 142(18), 3126-3137. https://doi.org/10.1242/dev.120063

Bastidas-Ponce, A., Scheibner, K., Lickert, H., & Bakhti, M. (2017). Cellular and molecular mechanisms coordinating pancreas development. Development (Cambridge, England), 144(16), 2873-2888. https://doi.org/10.1242/dev.140756

Jennings, R. E., Berry, A. A., Kirkwood-Wilson, R., Roberts, N. A., Hearn, T., Salisbury, R. J., Blaylock, J., Piper Hanley, K., & Hanley, N. A. (2013). Development of the human pancreas from foregut to endocrine commitment. Diabetes, 62(10), 3514-3522. https://doi.org/10.2337/db12-1479

Sinagoga, K. L., McCauley, H. A., Múnera, J. O., Reynolds, N. A., Enriquez, J. R., Watson, C., Yang, H. C., Helmrath, M. A., & Wells, J. M. (2018). Deriving functional human enteroendocrine cells from pluripotent stem cells. Development, 145(19), dev165795. https://doi.org/10.1242/dev.165795

Brissova, M., Fowler, M. J., Nicholson, W. E., Chu, A., Hirshberg, B., Harlan, D. M., & Powers, A. C. (2005). Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 53(9), 1087-1097. https://doi.org/10.1369/jhc.5C6684.2005

Quesada, I., Tudurí, E., Ripoll, C., & Nadal, A. (2008). Physiology of the pancreatic alpha-cell and glucagon secretion: role in glucose homeostasis and diabetes. The Journal of endocrinology, 199(1), 5-19. https://doi.org/10.1677/JOE-08-0290

Unger, R. H., & Cherrington, A. D. (2012). Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. The Journal of clinical investigation, 122(1), 4-12. https://doi.org/10.1172/JCI60016

Christensen, M., Bagger, J. I., Vilsbøll, T., & Knop, F. K. (2011). The alpha-cell as target for type 2 diabetes therapy. The review of diabetic studies : RDS, 8(3), 369-381. https://doi.org/10.1900/RDS.2011.8.369

Ivanenko, T. V., & Abramov, A. V. (2022). Optimization of endocrine pancreas fluorescence analysis using machine methods. Pathologia, 19(1), 24-31. https://doi.org/10.14739/2310-1237.2022.1.254173

Kolesnyk, Yu. M., Abramova, T. V., Ivanenko, T. V., & Abramov, A. B. (2018). Porivnialna kharakterystyka populiatsii endokrynotsytiv pidshlunkovoi zalozy u shchuriv linii WISTAR i SHR zi streptozototsyn-indukovanym diabetom [Comparative characteristics of the pancreatic endocrinocyte population in WISTAR and SHR rats with streptozotocin-induced diabetes]. Intehratyvni mekhanizmy patolohichnykh protsesiv: vid eksperymentalnykh doslidzhen do klinichnoi praktyky. Materials of the VII Plenum of the Ukrainian Scientific Society of Pathophysiologists] (pp. 44-45). [in Ukrainian].

Unger, R. H., & Orci, L. (1975). The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet, 1(7897), 14-16. https://doi.org/10.1016/s0140-6736(75)92375-2

Omar-Hmeadi, M., Lund, P. E., Gandasi, N. R., Tengholm, A., & Barg, S. (2020). Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes. Nature communications, 11(1), 1896. https://doi.org/10.1038/s41467-020-15717-8

Kawamori, D., Kurpad, A. J., Hu, J., Liew, C. W., Shih, J. L., Ford, E. L., Herrera, P. L., Polonsky, K. S., McGuinness, O. P., & Kulkarni, R. N. (2009). Insulin signaling in alpha cells modulates glucagon secretion in vivo. Cell metabolism, 9(4), 350-361. https://doi.org/10.1016/j.cmet.2009.02.007

Kawamori, D., Akiyama, M., Hu, J., Hambro, B., & Kulkarni, R. N. (2011). Growth factor signalling in the regulation of α-cell fate. Diabetes, obesity & metabolism, 13 Suppl 1, 21-30. https://doi.org/10.1111/j.1463-1326.2011.01442.x

Elliott, A. D., Ustione, A., & Piston, D. W. (2015). Somatostatin and insulin mediate glucose-inhibited glucagon secretion in the pancreatic α-cell by lowering cAMP. American journal of physiology. Endocrinology and metabolism, 308(2), E130-E143. https://doi.org/10.1152/ajpendo.00344.2014

Patel, Y. C., Amherdt, M., & Orci, L. (1982). Quantitative electron microscopic autoradiography of insulin, glucagon, and somatostatin binding sites on islets. Science, 217(4565), 1155-1156. https://doi.org/10.1126/science.6126003

Feng, A. L., Xiang, Y. Y., Gui, L., Kaltsidis, G., Feng, Q., & Lu, W. Y. (2017). Paracrine GABA and insulin regulate pancreatic alpha cell proliferation in a mouse model of type 1 diabetes. Diabetologia, 60(6), 1033-1042. https://doi.org/10.1007/s00125-017-4239-x

Abramova, T. V., & Kolesnyk, Yu. M. (2017). Osobennosti organizatsii populyatsii al'fa-kletok v podzheludochnoi zheleze u krys so spontannoi gipertenzii (SHR) [Features of the alpha-cell population organization in pancreas of spontaneously hypertensive rats (SHR)]. Pathologia, 14(2), 124-128. [in Russian]. https://doi.org/10.14739/2310-1237.2017.2.109249

Naya, F. J., Huang, H. P., Qiu, Y., Mutoh, H., DeMayo, F. J., Leiter, A. B., & Tsai, M. J. (1997). Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Genes & development, 11(18), 2323-2334. https://doi.org/10.1101/gad.11.18.2323

Hussain, M. A., Miller, C. P., & Habener, J. F. (2002). Brn-4 transcription factor expression targeted to the early developing mouse pancreas induces ectopic glucagon gene expression in insulin-producing beta cells. The Journal of biological chemistry, 277(18), 16028-16032. https://doi.org/10.1074/jbc.M107124200

Ivanenko, T. V. (2011). Vliyaniye gipoksicheskikh trenirovok na funktsiyu beta-kletok pankreaticheskikh ostrovkov [Effect of hypoxic training on functioning of pancreatic islet beta-cells]. Aktualni problemy suchasnoi medytsyny: Visnyk ukrainskoi medychnoi stomatolohichnoi akademii, 11(4), 82-84. [in Russian].

Published

2023-03-10

How to Cite

1.
Ivanenko TV. Analysis of the activity of c-kit immunopositive alpha-cells of the pancreas in exogenous infusions and endogenously formed pathology. Current issues in pharmacy and medicine: science and practice [Internet]. 2023Mar.10 [cited 2024Oct.10];16(1):47-52. Available from: http://pharmed.zsmu.edu.ua/article/view/273223

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Original research