Metformin modulates survival, oxidative stress, and gene expression in a high-sucrose Drosophila diabetes model

Background Excess dietary sugar is a major contributor to metabolic disorders, including type 2 diabetes mellitus (T2DM). This study investigates the physiological, biochemical, behavioral, and molecular effects of high-sucrose diets in Drosophila melanogaster and evaluates the modulatory effects of metformin under these conditions. Methods Flies were reared on normal and high-sucrose diets (5% and 15%), with or without metformin treatment (5 mM and 15 mM). Pupation, survival, locomotor activity (negative geotaxis), trehalose levels, antioxidant enzyme activities (SOD, GST), and expression of stress-related genes (Mn-SOD, Cu/Zn-SOD, MTH, CAT, Hsp40, Hsp70) were assessed after 10 days of treatment. Gene expression levels were quantified relative to the normal control group using RpS20 as the housekeeping reference. Results High-sucrose diets significantly reduced pupation and survival rates, impaired locomotor performance, increased trehalose levels, and decreased antioxidant enzyme activities. These diets were also associated with downregulation of stress- and antioxidant-related genes. Metformin treatment partially attenuated several of these alterations relative to the corresponding sucrose-treated groups, including improvements in pupation, survival, locomotor performance, metabolic parameters, antioxidant enzyme activity, and gene expression. Conclusion High-sucrose diets induced metabolic disturbances in Drosophila melanogaster , including impaired developmental progression and survival, functional locomotor impairment, carbohydrate imbalance, oxidative stress, and suppression of stress-related gene expression. Metformin partially attenuated several of these changes within the corresponding sucrose-treatment groups. These findings support the utility of Drosophila melanogaster as a tractable model for studying diet-induced metabolic dysfunction and evaluating pharmacological interventions.