Metformin modulates survival, oxidative stress, and gene expression in a high-sucrose Drosophila diabetes model
- 1Biology Department, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates
Abstract
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.
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BibTeX
@article{lotfy2026metformin,
title = {{Metformin modulates survival, oxidative stress, and gene expression in a high-sucrose Drosophila diabetes model}},
author = {Mohamed Lotfy and Fatema Al Sawai and Dhoha Alyammahi and Biduth Kundu},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0359638},
url = {https://doi.org/10.1371/journal.pone.0359638},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Metformin modulates survival, oxidative stress, and gene expression in a high-sucrose Drosophila diabetes model
AU - Mohamed Lotfy
AU - Fatema Al Sawai
AU - Dhoha Alyammahi
AU - Biduth Kundu
PY - 2026
DA - 2026/10/01
JO - PLOS One
DO - 10.1371/journal.pone.0359638
UR - https://doi.org/10.1371/journal.pone.0359638
AB - 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.
SN - 1932-6203
ER -