Aspirin-Mediated Reduction of Glucose Level and Inflammation in Drosophila melanogaster

Abstract

Diabetes mellitus (DM), particularly type 2 diabetes mellitus (T2DM), is a global health challenge marked by chronic hyperglycemia and inflammation, which contributes to both metabolic dysregulation and associated complications. Inflammation exacerbates T2DM by activating immune signaling pathways and promoting insulin resistance. This study aims to investigate the interplay between hyperglycemia and inflammation and to explore the therapeutic potential of aspirin in mitigating these processes using Drosophila melanogaster as a model organism. We utilized the PGRP-LB ^Δ strain, which exhibits dysregulated immune responses due to the loss of the PGRP-LB gene, leading to a phenotype resembling human autoinflammatory conditions. Larvae of the PGRP-LB ^Δ were fed a high-sucrose diet to induce increased glucose levels, mimicking the metabolic disturbances of T2DM. Aspirin, at different concentrations, was administered to assess its effects on high glucose level-induced inflammation. The results demonstrated that aspirin significantly improved hemolymph glucose levels, larval size, weight, and development. Additionally, aspirin enhanced larval mobility and reduced glucose level-associated immune dysfunction, as evidenced by changes in the expression of key immune and insulin-related genes. These findings highlight the utility of D. melanogaster as an effective and cost-efficient model to investigate the molecular mechanisms of T2DM and inflammation. The study also provides preliminary evidence for the potential of aspirin as an anti-inflammatory agent to modulate glucose levels and inflammation in T2DM, offering a promising avenue for therapeutic development.

Figure 1

Experimental design. Six groups of 3rd instar larvae were given fly food containing a normal diet, HSD, HSD + EtOH, or HSD + ASA (0.05 μM, 0.5 μM, and 5 μM). ASA, acetylsalicylic acid; EtOH, ethanol; HSD, high-sugar diet.

Figure 2

Increased glucose level following aspirin treatment. The glucose level in the larval body increased due to HSD induction (A), while aspirin treatment effectively reduced the glucose level in a dose-dependent manner (B). The reduction in the glucose level is associated with the regulation of gene expression of drs (C), attaA (D), dilp3 (E), and dilp6 (F). ND, normal diet; HSD, high-sugar diet; EtOH, ethanol; ASA, aspirin; ns, nonsignificant; *, p < 0.05; **, p < 0.01; ****, and p < 0.0001 (means ± SD, n = 3).

Figure 3

Improvement in body size, body weight, and crawling activity after aspirin administration. HSD exposure is capable of reducing body size, weight, and crawling activity. After aspirin administration, it effectively increases body length (A), body width (B), body weight (C), and crawling activity (D). ND, normal diet; HSD, high-sugar diet; ASA, aspirin; ns, nonsignificant; *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, and p < 0.0001 (means ± SD, n = 3).

Figure 4

Improvement in survival after aspirin administration but not in fecundity. HSD exposure was able to reduce the survival from larva to adult fly and fecundity. After aspirin administration, it effectively improved the survival from larva to pupa (A) and improved the survival from pupa to adult fly (B) but not in fecundity (C). ND, normal diet; HSD, high-sugar diet; ASA, aspirin; ns, nonsignificant; *, p < 0.05; **, p < 0.01 (means ± SD, n = 3).