Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2023; 69(5): 51-60


T.R. Kerimov1, S.I. Savosko2, S.M. Smirnov1 L.V. Natrus2

  1. Luhansk State Medical University, Rivne, Ukraine 2Bogomolets National Medical University, Kyiv, Ukraine


Type 2 diabetes mellitus (T2DM) is associated with a number of complications, in particular, gastrointestinal tract dysfunction. Impaired mucin secretion by the gastric mucosa in rats with T2DM may affect the absorption of drugs in the stomach and may explain the poor efficacy of treatment and correction of the condition. The aim of our work was to study changes in mucin secretion by the mucous membrane of the gastric fundus in rats with T2DM and the administration of metformin in combination with propionate. T2DM was modelled in rats by a high-fat diet for 3 months with a single administration of streptozotocin (25 mg/kg). Pharmacological correction was performed by intragastric administration of metformin (60 mg/ kg), propionate (60 mg/kg), and combined administration of the mentioned drugs for 14 days. Structural changes in the gastric mucosa and mucopolysaccharide secretion activity were assessed by histochemistry. Western blot analysis of MUC5AC expression was performed. A significant decrease in mucin production was observed in the lower stomach of rats, which was associated with a decrease in the density of cells actively producing acidic mucopolysaccharides. Metformin administration to animals with T2DM did not restore mucin production in the gastric fundus, whereas propionate administration increased acid mucopolysaccharide secretion. An increase in the neutral component of mucus and MUC5AC was found in T2DM. The combined administration of metformin and propionate helped to reduce the content of this mucin. The identified morphofunctional changes in the gastric fundus require further research and should be taken into account when using oral hypoglycaemic drugs because the loss of the mucin barrier layer may affect the state of the gastric mucosa and the absorption of drugs.

Keywords: diabetes; stomach; mucin; metformin; propionate; MUC5AC; neutral and acidic mucus components.


  1. Pellegrini S, Sordi V, Bolla AM, Saita D, et al. duodenal mucosa of patients with type 1 diabetes shows distinctive inflammatory profile and microbiota. J Clin Endocrinol Metab. 2017;102(5):1468-77. CrossRef PubMed
  2. Li WZ, Stirling K, Yang JJ, Zhang L. Gut microbiota and diabetes: From correlation to causality and mechanism. World J Diabet. 2020;11(7):293-308. CrossRef PubMed PubMedCentral
  3. Concepción Zavaleta MJ, Gonzáles Yovera JG, Moreno Marreros DM, et al. Diabetic gastroenteropathy: An underdiagnosed complication. World J Diabet. 2021;12(6):794-809. CrossRef PubMed PubMedCentral
  4. Krishnan B, Babu S, Walker J, Walker AB, Pappachan JM. Gastrointestinal complications of diabetes mellitus. World J Diabet. 2013;4(3):51-63. CrossRef PubMed PubMedCentral
  5. Bharucha AE, Locke GR, Murray JA. Gastrointestinal Manifestations of Diabetes. In: Cowie CC, Casagrande SS, Menke A, et al., editors. Diabetes in America. 3rd ed. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (US); 2018 Aug. CHAPTER 7. PMID: 33651548.
  6. Farmer AD, Bruckner-Holt C, Schwartz S, Sadler E, Kadirkamanthan S. Diabetic gastroparesis: Perspectives from a patient and health care providers. J Patient Cent Res Rev. 2019;6(2):148-57. CrossRef PubMed PubMedCentral
  7. Falavigna M, Stein PC, Flaten GE, di Cagno MP. Impact of Mucin on drug diffusion: development of a straightforward in vitro method for the determination of drug diffusivity in the presence of mucin. Pharmaceutics. 2020;12(2):168. CrossRef PubMed PubMedCentral
  8. Nankova BB, Agarwal R, MacFabe DF, La Gamma EF. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cellspossible relevance to autism spectrum disorders. PLoS One. 2014;9(8):e103740. CrossRef PubMed PubMedCentral
  9. Natrus LV, Osadchuk YS, Lisakovska OO, Labudzinskyi DO, Klys YG, Chaikovsky YB. Effect of propionic acid on diabetes-induced impairment of unfolded protein response signaling and astrocyte/microglia crosstalk in rat ventromedial nucleus of the hypothalamus. Neural Plast. 2022; 22:6404964. CrossRef PubMed PubMedCentral
  10. Kasarello K, Cudnoch-Jedrzejewska A, Czarzasta K. Communication of gut microbiota and brain via immune and neuroendocrine signaling. Front Microbiol. 2023; 25;14:1118529. CrossRef PubMed PubMedCentral
  11. Grabovoy AN, Yaremenko LM. Method of quantitative assessment of immunohistochemical reactions. Utility model patent 147216, G01N 33/48 (2006.01), G01N 33/53 (2006.01) [Ukrainian] CrossRef
  12. Kang Y, Park H, Choe BH, Kang B. The role and function of mucins and its relationship to inflammatory bowel disease. Front Med (Lausanne). 2022;9:848344. CrossRef PubMed PubMedCentral
  13. Takeuchi K, Ueshima K, Ohuchi T, Okabe S. Induction of gastric lesions and hypoglycemic response by food deprivation in streptozotocin-diabetic rats. Dig Dis Sci 1994; 39: 626-34. CrossRef PubMed
  14. MacDonald A, Dekanski JB, Gottfried S, Parke DV, Sacra P. Effects of blood glucose levels on aspirin-induced gastric mucosal damage. Am J Dig Dis. 1977;22(10):909-14. CrossRef PubMed
  15. Miranda MCG, Oliveira RP, Torres L, Aguiar SLF, Pinheiro-Rosa N, Lemos L, Guimarães MA, Reis D, Silveira T, Ferreira Ê, Moreira TG, Cara DC, Maioli TU, Kelsall BL, Carlos D, Faria AMC. Frontline science: Abnormalities in the gut mucosa of non-obese diabetic mice precede the onset of type 1 diabetes. J Leukoc Biol. 2019;106(3):513-29. CrossRef PubMed
  16. Tkachuk OV, Tkachuk SS, Povar MA, Anokhina SI, Yasinska OV, Vadziuk SN. Peculiarities of systemic pathobiochemical reactions to brain ischemia-reperfusion in rats with diabetes mellitus. Fiziol Zh. 2022; 68(4): 40-7. CrossRef
  17. Daft JG, Lorenz RG. Role of the gastrointestinal ecosystem in the development of type 1 diabetes. Pediatr Diabet. 2015;16(6):407-18. CrossRef PubMed PubMedCentral
  18. Paone P, Cani PD. Mucus barrier, mucins and gut microbiota: the expected slimy partners? Gut. 2020; 69(12):2232-43. CrossRef PubMed PubMedCentral
  19. Benson KK, Sheel A, Rahman S, Esnakula A, Manne A. Understanding the clinical significance of MUC5AC in biliary tract cancers. Cancers. 2023; 15(2):433. CrossRef PubMed PubMedCentral
  20. Saraei P, Asadi I, Kakar MA, Moradi-Kor N. The beneficial effects of metformin on cancer prevention and therapy: a comprehensive review of recent advances. Cancer Manag Res. 2019;11:3295-313. CrossRef PubMed PubMedCentral
  21. Zhang K; Bai P, Dai H, Deng Z. Metformin and risk of cancer among patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Prim Care Diabet 2021, 15, 52-8. CrossRef PubMed
  22. Zheng, J, Xie SH, Santoni G, Lagergren J. Metformin use and risk of gastric adenocarcinoma in a Swedish population-based cohort study. Br J Cancer. 2019, 121, 877-82. CrossRef PubMed PubMedCentral
  23. de la Cuesta-Zuluaga J, Mueller NT, Corrales-Agudelo V, et al. Metformin Is associated with higher relative abundance of mucin-degrading akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diabet Care. 2017;40(1):54-62. CrossRef PubMed
  24. Forslund K, Hildebrand F, Nielsen T, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262-66. CrossRef PubMed PubMedCentral
  25. Du L, Li Q, Yi H, Kuang T, Tang Y, Fan G. Gut microbiotaderived metabolites as key actors in type 2 diabetes mellitus. Biomed Pharmacother. 2022;149:112839. CrossRef PubMed
  26. Wu Q, Dong J, Bai X, Jiang Y, Li J, Fan S, Cheng Y, Jiang G. Propionate ameliorates diabetes-induced neurological dysfunction through regulating the PI3K/Akt/eNOS signaling pathway. Eur J Pharmacol. 2022;925:174974. CrossRef PubMed

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.