Aim: The combined impact of traditional and non-traditional risk factors of type 2 diabetes (T2D) on the development and progression of insulin resistance and associated complications is poorly understood. Therefore, we assessed the effect of moderately rich sugar diet coupled with environmental chemical exposure on the development and progression of T2D using Drosophila as a model organism.
Main methods: We reared newly eclosed Drosophila males on a diet containing atrazine (20 μg/ml; non-traditional risk factor) and/or moderately high sucrose (0.5 M/1 M; to mimic binge eating, Traditional risk factor) for 20-30 days. Subsequently, we assessed diabetic parameters, oxidative stress parameters and also the abundance of advanced glycation end products (AGEs) along with their receptor (RAGE) in these flies. For diabetic cardiomyopathy, we examined the pericardin (tissue fibrosis marker) level in Drosophila heart.
Key findings: Flies reared on 20 μg/ml atrazine alone showed T2D hallmarks at 30 days. In contrast, flies reared on 0.5 M sucrose+ 20 μg/ml atrazine showed insulin resistance characterized by hyperglycemia and increased Drosophila insulin-like peptides along with reduced insulin signaling at 20 days, similar to those reared on high sucrose diet. In addition, both groups had high levels of oxidative stress and showed starvation response (converting triglycerides into fatty acids). Alarmingly, flies fed with sucrose+atrazine for 20 and 30 days had elevated pericardin in heart tissues, indicating early onset of diabetic complications such as cardiomyopathy.
Significance: Lifestyle-chemical exposure synergistically impairs glucose metabolism, affects organisms' redox state and leads to the early onset of T2D and associated complications like cardiomyopathy.
Keywords: Cardiomyopathy; Herbicide; Insulin resistance; Oxidative stress; Starvation response; Xenobiotics.
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