THE PRENATAL DEVELOPMENT OF THE SPINY MICE (ACOMYS) PANCREATIC ENDOCRINE APPARATUS: Α- AND Δ-CELLS APPEAR EARLIER THAN Β-CELLS
https://doi.org/10.20340/mv-mn.2023.31(4).808
Abstract
All over the world, work is actively underway to study the histogenesis and organogenesis of the pancreas, which makes it possible to answer a number of questions related to the mechanisms of this organ regeneration following damage of various origins. Spiny mice (Acomys) are a convenient laboratory model for studying prenatal development of internal organs because they have a relatively long intrauterine development period. These mice are predisposed to developing diabetes with obesity, hyperglycemia, glycosuria and ketonuria without insulin resistance under high-energy feeding conditions. The purpose of the study is the sequence of appearance and distribution of insulin-, glucagon- and somatostatin-positive cells to analyze the morphogenesis of the pancreatic islet apparatus during the prenatal development of spiny mice at different stages of gestation. The work was carried out on Spiny mice (Acomys). The 15th, 19th, 22nd, 24th, 28th, 34th, and 38th days of gestation were studied. The expression of glucagon, insulin and somatostatin in the developing pancreas was studied by immunohistochemistry methods. The first glucagon- and somatostatin-positive cells were found on the 19th day of prenatal development, and insulin-positive cells on the 22nd day. The first accumulations of endocrine cells appear on the 22nd day of gestation. The islets of Langerhans are clearly visible from the 34th day of prenatal development. In Spiny mice, during prenatal development in the pancreas, α- and δ-cells appear earlier than β-cells of the islets of Langerhans. The morphology of α-, β- and δ-cells and localization in pancreatic islets in humans and Acomys mice during prenatal development is similar. We believe that data on the development of the endocrine apparatus of the pancreas obtained in Spiny mice can be extrapolated to humans and the results of the work can clarify the processes of differentiation of endocrine cells of the islets of Langerhans in the human pancreas.
About the Authors
Kadriya N. SultanovaRussian Federation
Senior Lecturer of the Department of Morphology and General Pathology
Competing Interests:
The Author declares that she did have no conflicts of interest in planning, implementing, financing and using the results of this study
Il'ya S. Neofitov
Russian Federation
Laboratory Assistant-Researcher of the Department of Morphology and General Pathology
Competing Interests:
The Author declares that he did have no conflicts of interest in planning, implementing, financing and using the results of this study
Angelina A. Titova
Russian Federation
Candidate of Medical Sciences, Senior Lecturer of the Department of Morphology and General Pathology
Competing Interests:
The Author declares that she did have no conflicts of interest in planning, implementing, financing and using the results of this study
Ayrat I. Bilyalov
Senior Lecturer of the Department of Morphology and General Pathology
Competing Interests:
The Author declares that he did have no conflicts of interest in planning, implementing, financing and using the results of this study
Roman V. Ursan
Russian Federation
Senior Lecturer of the Department of Morphology and General Pathology
Competing Interests:
The Author declares that he did have no conflicts of interest in planning, implementing, financing and using the results of this study
Dina I. Andreeva
Russian Federation
Candidate of Medical Sciences, Associate Professor of the Department of Morphology and General Pathology
Competing Interests:
The Author declares that she did have no conflicts of interest in planning, implementing, financing and using the results of this study
Maxim S. Kaligin
Russian Federation
Docent, Candidate of Medical Sciences, Associate Professor of the Department of Morphology and General Pathology
Competing Interests:
The Author declares that he did have no conflicts of interest in planning, implementing, financing and using the results of this study
Andrey P. Kiyasov
Russian Federation
Professor, Doctor of Medical Sciences, Director of the Institute of Fundamental Medicine and Biology
Competing Interests:
The Author declares that he did have no conflicts of interest in planning, implementing, financing and using the results of this study
References
1. Grapin-Botton A, Kim YH. Pancreas organoid models of development and regeneration. Development. 2022;149(20):dev201004. DOI: 10.1242/dev.201004
2. Ma Z, Zhang X, Zhong W, et al. Deciphering early human pancreas development at the single-cell level. Nat Commun. 2023;14(1):5354. DOI: 10.1038/s41467-023-40893-8
3. Proshchina AE, Krivova YS, Barabanov VM, Saveliev SV. Pancreatic endocrine cell arrangement during human ontogeny. Acta Histochem. 2019;121(5):638-645. DOI:10.1016/j.acthis.2019.05.010
4. Jennings RE, Berry AA, Kirkwood-Wilson R, et al. Development of the human pancreas from foregut to endocrine commitment. Diabetes. 2013;62(10):3514–3522. DOI :10.2337/db12-1479
5. Kaligin MS, Gumerova AA, Titova MA, i dr. C-kit markyor stvolovykh kletok endokrinotsitov podzheludochnoy zhelezy cheloveka. Morfologija. 2011;140(4):32–37. In Russian
6. Miretskaya EI. Biomeditsinskie issledovaniya na cheloveke: pravovye i moral'no-eticheskie problemy. Yuridicheskaya nauka i praktika: Vestnik Nizhegorodskoy akademii MVD Rossii. 2014;2(26):235–237. In Russian
7. Pinheiro G, Prata DF, Araújo IM, Tiscornia G. The African spiny mouse (Acomys spp.) as an emerging model for development and regeneration. Lab Anim. 2018;52(6):565–576. DOI: 10.1177/0023677218769921
8. Dickinson H, Walker DW, Cullen-McEwen L, et al. The spiny mouse (Acomys cahirinus) completes nephrogenesis before birth. Am J Physiol Renal Physiol. 2005;289(2):F273–9. DOI :10.1152/ajprenal.00400.2004
9. Vieira E, Salehi A, Gylfe E. Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells. Diabetologia. 2007;50(2):370–379. DOI: 10.1007/s00125-006-0511-1
10. Brereton MF, Vergari E, Zhang Q, Clark A. Alpha-, Delta- and PP-cells: Are They the Architectural Cornerstones of Islet Structure and Co-ordination? J Histochem Cytochem. 2015;63(8):575–591. DOI: 10.1369/0022155415583535
11. Steiner DJ, Kim A, Miller K, Hara M. Pancreatic islet plasticity: interspecies comparison of islet architecture and composition. Islets. 2010;2(3):135–145. DOI: 10.4161/isl.2.3.11815
12. Kilimnik G, Zhao B, Jo J, et al. Altered islet composition and disproportionate loss of large islets in patients with type 2 diabetes. PLoS One. 2011;6(11):e27445. DOI: 10.1371/journal.pone.0027445
13. Herrera PL, Huarte J, Sanvito F, et al. Embryogenesis of the murine endocrine pancreas; early expression of pancreatic polypeptide gene. Development. 1991;113(4):1257–1265. DOI: 10.1242/dev.113.4.1257
14. Pan FC, Wright C. Pancreas organogenesis: from bud to plexus to gland. Dev Dyn. 2011;240(3):530–565. DOI :10.1002/dvdy.22584
15. Larsson LI. On the development of the islets of Langerhans. Microsc Res Tech. 1998;43(4):284–291. DOI: 10.1002/(SICI)1097-0029(19981115)43:4<284::AID-JEMT2>3.0.CO;2-0
16. Collombat P, Xu X, Heimberg H, Mansouri A. Pancreatic beta-cells: from generation to regeneration. Semin Cell Dev Biol. 2010;21(8):838–844. DOI: 10.1016/j.semcdb.2010.07.007
17. Talchai C, Xuan S, Lin HV, et al. Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell. 2012;150(6):1223–1234. DOI: 10.1016/j.cell.2012.07.029
18. Proshchina A, Krivova Yu, Gurevich L, et al. 2153-P: PDX1- and Nkx6.1-Immunonegative ß Cells in the Developing Human Pancreas. Diabetes. 2019;68(1):2153-P. DOI: 10.2337/db19-2153-P
19. Proshhina AE, Krivova JuS, Otlyga DA i dr. Osobennosti raspredeleniya transkriptsionnogo faktora Pdx1 v kletkakh podzheludochnoy zhelezy v prenatal'nom razvitii cheloveka. Klinicheskaya i eksperimental'naya morfologiya. 2019;8(1):32-38. In Russian. DOI: 10.31088/2226-5988-2019-29-1-32-38
20. Habener JF, Stanojevic V. α-cell role in β-cell generation and regeneration. Islets. 2012;4(3):188–198. DOI: 10.4161/isl.20500
21. Collombat P, Mansouri A, Hecksher-Sorensen J, et al. Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev. 2003;17(20):2591–25603. DOI: 10.1101/gad.269003
22. Herrera PL. Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. Development. 2000;127(11):2317–2322. DOI: 10.1242/dev.127.11.2317
23. Prasadan K, Shiota C, Xiangwei X, et al. A synopsis of factors regulating beta cell development and beta cell mass. Cell Mol Life Sci. 2016;73(19):3623–3637. DOI: 10.1007/s00018-016-2231-0
24. Ul'yanovskaja S.A. Prenatal'ny i ranny postnatal'ny morfogenez podzheludochnoy zhelezy cheloveka. Fundamental'nye issledovaniya. 2013;9(3):530–534. In Russian
25. Ye L, Robertson MA, Hesselson D, et al. Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis. Development. 2015;142(8):1407–1417. DOI :10.1242/dev.117911
26. Haughton CL, Gawriluk TR, Seifert AW. The Biology and Husbandry of the African Spiny Mouse (Acomys cahirinus) and the Research Uses of a Laboratory Colony. J Am Assoc Lab Anim Sci. 2016;55(1):9–17
27. Gelling RW, Du XQ, Dichmann DS, et al. Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice. Proc Natl Acad Sci USA. 2003;100(3):1438–1443. DOI: 10.1073/pnas.0237106100
28. Gu W, Yan H, Winters KA, et al. Long-term inhibition of the glucagon receptor with a monoclonal antibody in mice causes sustained improvement in glycemic control, with reversible alpha-cell hyperplasia and hyperglucagonemia. J Pharmacol Exp Ther. 2009;331(3):871–881. DOI: 10.1124/jpet.109.157685
29. Vuguin PM, Kedees MH, Cui L, et al. Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation. Endocrinology. 2006;147(9):3995–4006. DOI: 10.1210/en.2005-1410
30. Kieffer TJ, Habener JF. The glucagon-like peptides. Endocr Rev. 1999;20(6):876–913. DOI: 10.1210/edrv.20.6.0385
31. Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol. 2009;5(5):262–269. DOI: 10.1038/nrendo.2009.48
32. Wilson ME, Kalamaras JA, German MS. Expression pattern of IAPP and prohormone convertase 1/3 reveals a distinctive set of endocrine cells in the embryonic pancreas. Mech Dev. 2002;115(1-2):171–176. DOI: 10.1016/s0925-4773(02)00118-1
33. Kedees MH, Guz Y, Vuguin PM, et al. Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling. Dev Dyn. 2007;236(4):1126–1133. DOI: 10.1002/dvdy.21112
34. Brubaker PL, Drucker DJ. Minireview: Glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology. 2004;145(6):2653–2659. DOI: 10.1210/en.2004-0015
35. Heller RS, Jenny M, Collombat P, et al. Genetic determinants of pancreatic epsilon-cell development. Dev Biol. 2005;286(1):217–224. DOI: 10.1016/j.ydbio.2005.06.041
36. Hauge-Evans AC, King AJ, Carmignac D, et al. Somatostatin secreted by islet delta-cells fulfills multiple roles as a paracrine regulator of islet function. Diabetes. 2009;58(2):403–411. DOI: 10.2337/db08-0792
Supplementary files
The authors showed that glucagon- and somatostatin-positive endocrine cells are the first to be detected during prenatal development of the pancreas of Acomys mice
Review
For citations:
Sultanova K.N., Neofitov I.S., Titova A.A., Bilyalov A.I., Ursan R.V., Andreeva D.I., Kaligin M.S., Kiyasov A.P. THE PRENATAL DEVELOPMENT OF THE SPINY MICE (ACOMYS) PANCREATIC ENDOCRINE APPARATUS: Α- AND Δ-CELLS APPEAR EARLIER THAN Β-CELLS. Morphological newsletter. 2023;31(4):40-47. (In Russ.) https://doi.org/10.20340/mv-mn.2023.31(4).808