Hyperglycemia-Induced Apoptosis and Phagocytosis Suppression in Drosophila
DOI:
https://doi.org/10.48048/tis.2026.11170Keywords:
Hyperglycemia, Apoptosis, Phagocytosis Receptors, Inflammation, Drosophila melanogaster, Hyperglycemia, Apoptosis, Phagocytosis receptors, Inflammation, Drosophila melanogasterAbstract
Hyperglycemia, characterized by elevated blood glucose levels, is a major risk factor for the development of type 2 diabetes mellitus and its associated complications, including organ dysfunction and immune system impairment. Oxidative stress induced by hyperglycemia is known to disrupt cellular immune mechanisms, including phagocytosis, which is crucial for eliminating pathogens and damaged cells. This study aimed to assess the effects of a high-sugar diet (HSD) on phenotypic traits, phagocytosis, and expression of immune-related genes in Drosophila melanogaster wild-type w1118 and mutant itgbn2, which serves as a model organism for hyperglycemia. A phenotypic assay was conducted by observing glucose levels, development, body weight, crawling, and activity, as well as molecular analysis using the RT-qPCR method. The results showed that HSD treatment significantly increased hemolymph glucose levels and reduced larvae body weight, crawling ability, and developmental progression to the pupae and adult stages. Molecular analysis revealed a significant upregulation of pro-apoptotic gene expression in w1118 larvae, rpr expression increased by approximately 9% (p < 0.05), while in the itgbn² mutant, the increase was more substantial, reaching about 21% (p < 0.01). The grim expression was also significantly elevated in itgbn² larvae by around 25% (p < 0.001). In contrast, the phagocytic receptor gene drpr was markedly downregulated in w1118 larvae, showing a 50% reduction under HSD (p < 0.0001). In contrast, no significant changes were observed in the itgbn² mutant, a phagocytosis receptor involved in the elimination of apoptotic cells, which may reflect limited activation of integrin associated signaling pathways necessary for transcriptional responsiveness under hyperglycemic stress. Overall, these findings suggest that hyperglycemia induced by an HSD is associated with increased apoptosis and reduced phagocytic activity, possibly through disrupted integrin-mediated signaling in the itgbn² mutant, which may contribute to cellular immune dysfunction under hyperglycemic conditions. This study offers new insights into the molecular mechanisms underlying immune dysregulation in hyperglycemic conditions, highlighting the therapeutic potential of targeting phagocytic pathways to prevent diabetes-related complications in the future.
HIGHLIGHTS
- A high-sugar diet triggers hyperglycemia-like symptoms in Drosophila
- Immune disruption was evident through reduced phagocytosis and increased apoptotic activity.
- The phagocytic receptor integrin βν plays an important role in glucose homeostasis.
- Integrin βν dysfunction leads to impaired cellular immunity under hyperglycemic conditions.
- These findings offer novel insights into the link between apoptosis, phagocytosis, and metabolic stress.
GRAPHICAL ABSTRACT
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