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Progress in Medical Sciences ISSN: 2577 - 2996
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Progress in Medical Sciences. 2024; 8(4):(120-147)
doi: doi.org/10.47363/PMS/2024(8)207


The Adaptive Mechanism of Liver in Response to Hyperglycemic Functional Stress in Alloxan Induced Diabetes

Diana Dzidziguri*, Ekaterine Bakuradze, Irina Modebadze, Merab Sepashvili, Giorgi Aleksanashvili, Tornike Gogolauri, Nino Kharaishvili and Manana Berulava

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Abstract
Background: Diabetes is a common disease that poses significant medical and socio-economic challenges due to its widespread prevalence and its impact on disability and life expectancy. Recent studies have demonstrated a reduction in high-ploidy (2c×2) hepatocytes within one month of injecting Alloxan or Streptozotocin in experimental models of diabetes mellitus. This phenomenon is attributed to decreased insulin levels, which regulate cytokinesis and consequently affect the number of high-ploidy cells during cytoskeletal reorganization. However, the dynamics between diploid and high-ploidy cells during the initial phase of the disease (within the first 48 hours), characterized by extreme changes in glucose concentration, have not been thoroughly investigated. This study aims to explore the liver's adaptive responses to hyperglycemic stress during the early stages of diabetes.


Research Objects and Materials: Adult white rats (130-150 g) were used as the experimental subjects. Diabetes mellitus was induced in the animals by administering alloxan (180 mg/kg) intraperitoneally. 

Methods: The alloxan-induced diabetes model was validated by measuring changes blood glucose concentration and in insulin-producing pancreatic cells through immunohistochemistry in both intact and experimental groups. The histoarchitecture of the experimental animals was assessed using H&E staining. The proliferative activity of liver tissue was evaluated using the colchicine mitotic index method and liver samples collected 24 and 48 hours later. The smears were stained using Feulgen stain for DNA-specific staining and examined microscopically, with the images analyzed using ImageJ software.

Results: Within 48 hours of Alloxan injection, hepatocyte mitotic activity remained unchanged. Conversely, a significant increase of 4c cells was observed within the liver (p<0.05). 

Conclusion: At the initial stage of hyperglycemia developed by Alloxan injection (48 hours after injection), the liver's ability to adapt in response to increased functional load is expressed in the quantitative increase of high-ploidy cells through the mechanism of endoreduplication.