REACTION OF ISLET AND EXTRA ISLET ENDOCRINOCYTES IN DIABETES TYPE 1 AND 2
DOI: 10.22138/2500-0918-2018-15-3-405-412
A.V. Belousova, K.V. Sokolova, I.F. Gette,S.Yu. Medvedeva, I.G. Danilova, V.A. Chereshnev
Institute of Immunology and Physiology, Yekaterinburg, Russian Federation;
Institute of Medical Cell Technologies, Yekaterinburg, Russian Federation
Abstract. The aim of the investigation. Models of type 1 and 2 diabetes were obtained to compare and evaluate pathological changes according to morphometry and biochemical tests.Materials and methods. Male Wistar rats were administered alloxan in a dosage of 170 mg/kg to simulate DM1. Nicotinamide (110 mg/kg) and streptozotocin (65 mg/kg) were administered to simulate DM2. The histological and immunohistochemical analyses of pancreatic sections were performed, biochemical parameters were tested. Results. The increase in glucose level in DM1 and DM2 was accompanied by a decrease in the pancreatic islets number, the ?-cells number and insulin concentration in ?-cells. In the DM1 model, a decrease in the number of islet ?-cells, insulin content in ?-cells and in extra-islet cells agglomerates was accompanied by a decrease in the plasma insulin level and the glycated hemoglobin accumulation. In the DM2 model, a decrease in the number of ?-cells and insulin deficiency in the islets were compensated by an increase in the number of single extra-islet insulin-synthesizing cells. Conclusion. The streptozotocin-nicotinamide model obtains pathogenetic changes similar these in type 2 diabetes, such as hyperglycemia with a normal level of insulin in the blood plasma, which is supported by an increase in the number of single extra-island insulin-synthesizing cells and the remaining normal insulin production in agglomerates of extra-island insulin-synthesizing cells. In the alloxan model, hyperglycemia is accompanied by the accumulation of glycated hemoglobin and urea, and the decrease in insulin production is noted not only in the islets, but also in agglomerates of extra-island insulin-synthesizing cells, which is confirmed by a reduced insulin level in rat blood plasma.
Keywords: diabetes mellitus, ?-cells, pancreatic islets, extra-islet insulin synthesizing cells
Received 05.04.2018
For citation:
A.V. Belousova A.V., K.V. Sokolova K.V., I.F. Gette I.F., S.Yu. Medvedeva S.Yu., I.G. Danilova I.G., V.A. Chereshnev V.A. Reaction of islet and extra islet endocrinocytes in diabetes type 1 and 2. Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2018, Vol. 15, no. 3, pp. 405–412. DOI: 10.22138/2500-0918-2018-15-3-405-412 (In Russ)
REFERENCES
1. Zaychik A.Sh., Churilov L.P. Pathophysiology. Vol. 2. Fundamentals of pathochemistry. St. Petersburg: Elbi-SPb. 2001. 687 p. (in Russ)
2. Chen T., Gao J., Xiang P., Chen Y., Ji J., Xie P., Wu H., Xiao W., Wei Y., Wang S., Lan .L., Ji H., Yan T. Protective effect of platycodin D on liver injury in alloxan-induced diabetic mice via regulation of Treg/Th17 balance. Int. Immunopharmacol. 2015; 26 (2): 338-348.
3. Like A.A., Rossini A.A. Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science. 1976; 193: 415–417.
4. Malaisse W. Alloxan toxicity to the pancreatic B-cell. Biochem Pharmacol. 1982; 31: 3527–3534.
5. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol. Res. 2001; 50: 536–546.
6. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes (Review). Diabetologia. 2008; 51: 216-226.
7. Mozheyko L.A. Experimental models for the study of diabetes mellitus. Part II. Surgical, Streptozotocin and Dithizone Diabetes. Journal of the Grodno State Medical University. 2013; 4: 5-10. (in Russ)
8. Spasov A.A., Voronkova M.P., Singur G.L., Cheplyaeva N.I., Chepurnova M.V. Экспериментальная модель сахарного диабета типа 2. Biomeditsina. 2011; 3: 12-18. (in Russ)
9. Sharma R., Dave V., Sharma S., Pankaj J., Sachdev Y. Experimental Models on Diabetes: A Comprehensive Review. International Journal of Advances in Pharmaceutical Sciences. 2013; 4: 1-8.
10. Islam M. S., Loots D.T. Experimental rodent models of type 2 diabetes: a review. Methods and Findings in Experimental and Clinical Pharmacology. 2009; 31: 249-261.
11. Mezza T., Kulkarni R.N. The regulation of pre- and post-maturational plasticity of mammalian islet cell mass. Diabetologia. 2014; 57(7): 1291-303.
12. Shimoda M., Chen S., Noguchi H., Matsumoto S., Grayburn P.A. Neurogenic differentiation 1 directs differentiation of cytokeratin 19-positive human pancreatic nonendocrine cells into insulin-producing cells. Transplant Proc. 2010; 42(6):2071-4. doi: 10.1016/j.transproceed.2010.05.114.
13. Yatoh S., Dodge R., Akashi T., Omer A., Sharma A., Weir G.C., Bonner-Weir S. Differentiation of affinity-purified human pancreatic duct cells to beta-cells. Diabetes. 2007; 56(7):1802-9. doi:10.2337/db06-1670.
14. Danilova I.G., Gette I.F. A method for modeling alloxan diabetes. Patent RF №2534411; 2014. (in Russ)
15. Balabolkin M.I., Klebanova E.M., Kremyanskaya V.M. Treatment of diabetes mellitus and its complications. Guide for doctors. M.: Meditsina. 2005. (in Russ)
16. Dedov I.I., Mel'nichenko G.A., Fadeev V.F. Endocrinology: a textbook for high schools. M.: GEOTAR-Media. 2007. (in Russ)
17. Yaglov V.V., Yaglova N.V. Actual problems of biology of pancreatic acino-insular cells. Vestnik Rossijskoj akademii medicinskih nauk. 2010; 7: 28-35. (in Russ)
Authors
Anna V. Belousova
Junior researcher
a1b2v3@mail.ru
Kseniya V. Sokolova
Research assistant
Kssokolova@bk.ru
Irina F. Gette
Cand. Sci. (Biolog.), Senior Researcher
i.goette@yandex.ru
Svetlana Yu. Medvedeva
Cand. Sci. (Med.), Leading Researcher
Medvedeva-ran@yandex.ru
Irina G. Danilova
Dr. Sci. (Biolog.), Professor, Head of the Laboratory
Ig-danilova@yandex.ru
Valerij A. Chereshnev
Dr. Sci. (Med.), Professor, Academician, Chief Researcher
secretar@iip.uran.ru
Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Laboratory of Morphology and Biochemistry
Russian Federation, 620049, Ekaterinburg, Pervomaiskaya str., 106