PROPIONIC ACID RESTORES MUCIN SECRETION IN THE GASTRIC FUNDUS IN AN EXPERIMENTAL MODEL OF TYPE 2 DIABETES
T.R. Kerimov1, S.I. Savosko2, S.M. Smirnov1 L.V. Natrus2
- Luhansk State Medical University, Rivne, Ukraine
2Bogomolets National Medical University, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz69.05.051
![](/images/cite.png)
Abstract
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.
References
- 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
- 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
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
- 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
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) http://ir.librarynmu.com/handle/123456789/5372. [Ukrainian]
CrossRef
- 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
- 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
- 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
- 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
- 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
- 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
- Paone P, Cani PD. Mucus barrier, mucins and gut microbiota: the expected slimy partners? Gut. 2020; 69(12):2232-43.
CrossRef
PubMed PubMedCentral
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
|