Features of morphological changes in the masseter muscle in diabetes mellitus under conditions of comorbidity

Authors

DOI:

https://doi.org/10.26641/1997-9665.2025.3.46-54

Keywords:

masticatory muscles, skeletal muscles, stress, diabetes mellitus, hypokinesia, anatomy, ultrastructure, pathology, histology.

Abstract

Diabetes mellitus remains one of the major global healthcare challenges due to its rapid growth, the development of complications, and high mortality rates, despite the emergence of novel therapeutic strategies and approaches. One of its complications is diabetic myopathy, which may develop and progress differently under comorbid conditions. The purpose of our study was to determine the patterns of morphological alterations in the masseter muscle of rats in experimental streptozotocin-induced diabetes mellitus (SIDM) under conditions of chronic immobilization stress (CIS). The material for the study consisted of masseter muscles obtained from 20 sexually mature 6-month-old male rats, which were equally divided into 4 groups: group 1 – comorbid pathology (SIDM + CIS), group 2 – SIDM, group 3 – CIS, group 4 – control animals. Tissue samples were collected on day 28 of the experiment. Histological, electron microscopic, and morphometric methods were applied, followed by statistical data analysis. Results and conclusion. It was established that SIDM induces damage to muscle fibers by the mechanism of vacuolar degeneration and colliquative necrosis. These alterations occur against the background of diabetic microangiopathy and result in muscle fibers atrophy. In conditions of hyperglycemia and impaired blood supply in rats of groups 1 and 2, the following changes were observed: a reduction in MFs area by 31–18%; an increase in mitochondrial volume density by 1.8–1.6 times (p<0.05 in all cases). A characteristic feature of muscle fibers damage in the masseter muscle under comorbid conditions was the development of aseptic inflammatory cellular infiltrates, MFs death through necroptosis and necrosis, fragmentation and lysis of myofibrils, leading to a decrease in their volume density by 11 % compared with controls. In rats exposed to CIS, mitochondrial remodeling was observed (elongation, reduced volume, and increased matrix density), accompanied by a 13 % reduction in mitochondrial volume density. Мuscle fibers underwent atrophic damage via ferroptosis, autolysis, and apoptosis, showing a tendency toward atrophy. Thus, CDM and CIS cause atrophy and damage of masseter muscle fibers manifested by vacuolar degeneration, necroptosis, necrosis, and the formation of aseptic inflammatory infiltrates. These alterations develop against the background of impaired muscle perfusion as a result of diabetic microangiopathy.

References

  1. IDF Diabetes Atlas 2025. Available from: https://diabetesatlas.org/
  2. Antar SA, Ashour NA, Sharaky M, Khattab M, Ashour NA, Zaid RT, et al. Diabetes mellitus: Classification, mediators, and complications; A gate to identify potential targets for the development of new effective treatments. Biomed Pharmacother Biomedecine Pharmacother. 2023;168:115734. doi: 10.1016/j.biopha.2023.115734.
  3. Gómez-Perez AM, Damas-Fuentes M, Cornejo-Pareja I, Tinahones FJ. Heart Failure in Type 1 Diabetes: A Complication of Concern? A Narrative Review. J Clin Med. 2021;10(19):4497. doi: 10.3390/jcm10194497.
  4. Merz KE, Thurmond DC. Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake. Compr Physiol. 2020;10(3):785. doi: 10.1002/ cphy.c190029.
  5. Du H, Ma Y, Wang X, Zhang Y, Zhu L, Shi S, et al. Advanced glycation end products induce skeletal muscle atrophy and insulin resistance via activating ROS-mediated ER stress PERK/FOXO1 signaling. Am J Physiol-Endocrinol Metab. 2023;324(3):279–87. doi: 10.1152/ajpendo.00218. 2022.
  6. DeFronzo RA, Tripathy D. Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes. Diabetes Care. 2009;32(2):157–63. doi: 10.2337/dc09-S302.
  7. Tammineni ER, Manno C, Oza G, Figueroa L. Skeletal muscle disorders as risk factors for type 2 diabetes. Mol Cell Endocrinol. 2025;599:112466. doi: 10.1016/j.mce.2025.112466. https://pubmed. ncbi.nlm.nih.gov/39848431/
  8. Bassi-Dibai D, Santos-de-Araújo AD, Dibai-Filho AV, Azevedo LFS de, Goulart C da L, Luz GCP, et al. Rehabilitation of Individuals With Diabetes Mellitus: Focus on Diabetic Myopathy. Front Endocrinol. 2022;13:869921. doi: 10.3389/fendo.2022.869921.
  9. Giha HA, Sater MS, Alamin OAO. Diabetes mellitus tendino-myopathy: epidemiology, clinical features, diagnosis and management of an overlooked diabetic complication. Acta Diabetol. 2022;59(7):871–83. doi: 10.1007/s00592-022-01860-9.
  10. Lee EJ, Jang HC, Koo KH, Kim HY, Lim JY. Mechanical Properties of Single Muscle Fibers: Understanding Poor Muscle Quality in Older Adults with Diabetes. Ann Geriatr Med Res. 2020;24(4):267–73. doi: 10.4235/agmr.20.0078.
  11. Travis C, Srivastava PS, Hawke TJ, Kalaitzoglou E, Stratmann B. Diabetic Bone Disease and Diabetic Myopathy: Manifestations of the Impaired Muscle-Bone Unit in Type 1 Diabetes. J Diabetes Res. 2022;2022:1–8. doi: 10.1155/2022/ 2650342.
  12. Deschênes SS, Burns RJ, Graham E, Schmitz N. Depressive symptoms and sleep problems as risk factors for heart disease: a prospective community study. Epidemiol Psychiatr Sci. 2019;29:50. doi: 10.1017/S2045796019000441.
  13. [Medical and psychological consequences of war-related distress in Ukraine: what can we expect and what should be taken into account when providing medical care?] Ukr Med J. 2022;150. Ukrainian. https://www.umj.com.ua/article/232297/mediko-psihologichni-naslidki-distresu-vijni-v-ukrayini-shho-mi-ochikuyemo-ta-shho-potribno-vrahovuvati-pri-nadanni-medichnoyi-dopomogi
  14. Park M, Katon WJ, Wolf FM. Depression and risk of mortality in individuals with diabetes: a meta-analysis and systematic review. Gen Hosp Psychiatry. 2013;35(3):217–25. doi: 10.1016/ j.genhosppsych.2013.01.006.
  15. Jung I, Kwon H, Park SE, Han KD, Park YG, Kim YH, et al. Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study. Diabetes Metab J. 2020;45(3):379–89. doi: 10.4093/dmj.2020.0008.
  16. Kim S, Kim G, Cho SH, Oh R, Kim JY, Lee YB, et al. Impact of mental disorders on the all-cause mortality and cardiovascular disease outcomes in adults with new-onset type 1 diabetes: A nationwide cohort study. Psychiatry Res. 2024;342:116228. doi: 10.1016/j.psychres.2024.116228.
  17. Levitsky VA, Zhurakivska OY, Miskiv VA, Zayats LM, Petriv RB, Yakymiv YM, et al., inventors; Ivano-Frankivsk National Medical University, assignee. Method for modeling type 1 diabetes mellitus in animals of different ages. Ukraine patent for utility model 62966. 2011. Ukrainian.
  18. Miskiv VA, Zhurakivska OY, Paliychuk IV, Ivantsiv OR, Sebro OG, Vasilyuk VM, Fedorak LV, Bagayluk LB, Tkachuk YL, Paliychuk VI, inventors; Ivano-Frankivsk National Medical University, assignee. Method for modeling chronic stress in experimental animals of different age groups. Ukraine patent for invention 125623. 04.05.2022. Ukrainian.
  19. Bagriy MM, Dibrova VA, Popadynets OG, Gryshchuk MI, authors; Bagriy MM, Dibrova A, editors. [Methods of histological research]. Vinnytsia: Nova Knyha; 2016. 328 p. Ukrainian. ISBN. 978-966-382-594-6
  20. Louhimies S. Directive 86/609/EEC on the Protection of Animals Used for Experimental and Other Scientific Purposes1. Altern Lab Anim. 2002;30(2):217–9. doi: 10.1177/ 026119290203002S36.
  21. Fang J qian, author. Handbook of medical statistics. Singapore: World scientific publishing; 2018. ISBN. 978-981-314-895-6.
  22. Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell Res. 2019;29(5):347–64. doi: 10.1038/s41422-019-0164-5.
  23. Li Y, Liu Y, Liu S, Gao M, Wang W, Chen K, et al. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies. Signal Transduct Target Ther. 2023;8(1):152. doi: 10.1038/s41392-023-01400-z.
  24. Jun L, Robinson M, Geetha T, Broderick TL, Babu JR. Prevalence and Mechanisms of Skeletal Muscle Atrophy in Metabolic Conditions. Int J Mol Sci. 2023;24(3):2973. doi: 10.3390/ijms24032973.
  25. Koh TJ, Bryer SC, Pucci AM, Sisson TH. Mice deficient in plasminogen activator inhibitor-1 have improved skeletal muscle regeneration. Am J Physiol Cell Physiol. 2005;289(1):217-23. doi: 10.1152/ajpcell.00555.2004.
  26. Moyer-Mileur LJ, Slater H, Jordan KC, Murray MA. IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes. J Bone Miner Res Off. J Am Soc Bone Miner Res. 2008;23(12):1884–91. doi: 10.1359/jbmr.080713.
  27. Farup J, Just J, Paoli F de, Lin L, Jensen JB, Billeskov T, et al. Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients. Cell Metab. 2021;33(11):2201. doi: 10.1016/j.cmet.2021. 10.001.
  28. Tsutsui H, Kinugawa S, Matsushima S, Yokota T. Oxidative stress in cardiac and skeletal muscle dysfunction associated with diabetes mellitus. J Clin Biochem Nutr. 2010;48(1):68. doi: 10.3164/jcbn.11-012FR.
  29. Krause MP, Riddell MC, Hawke TJ. Effects of type 1 diabetes mellitus on skeletal muscle: clinical observations and physiological mechanisms. Pediatr Diabetes. 2011;12(4):345–64. doi: 10.1111/j.1399-5448.2010.00699.x.
  30. Ramamurthy B, Larsson L. Detection of an aging-related increase in advanced glycation end products in fast- and slow-twitch skeletal muscles in the rat. Biogerontology. 2013;14(3):293–301. doi: 10.1007/s10522-013-9430-y.
  31. Hernández-Ochoa EO, Llanos P, Lanner JT. The Underlying Mechanisms of Diabetic Myopathy. J Diabetes Res. 2017;2017:1–3. doi: 10.1155/2017/7485738.
  32. Gomes LC, Benedetto GD, Scorrano L. During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol. 2011;13(5):589–98. doi: 10.1038/ncb2220.
  33. Leduc-Gaudet JP, Picard M, Pelletier FSJ, Sgarioto N, Auger MJ, Vallée J, et al. Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice. Oncotarget. 2015;6(20):17923–37. doi: 10.18632/oncotarget.4235.

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Published

2025-10-30

How to Cite

Habren-Syller , A.-N., & Zhurakivska , O. (2025). Features of morphological changes in the masseter muscle in diabetes mellitus under conditions of comorbidity. Морфологія / Morphologia / Morfologìâ, 19(3), 46–54. https://doi.org/10.26641/1997-9665.2025.3.46-54

Issue

Vol. 19 No. 3 (2025)

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