Impact of dietary modulations on the onset of Type 2 Diabetes in Drosophila melanogaster and its treatment mediated by metallic and polymeric nanoparticles

Abstract

Diabetes mellitus is one of the most prevalent metabolic disorders of the current century. High calorie diet having high glycemic index (GI) are the major contributors of diabetes. Due to the complex nature of this disease, it is difficult to treat and often leads to huge treatment burden. Numerous studies have tried to understand the detailed mechanism of this disease to design new and effective therapeutic approaches. The application of nanotechnology in the field of diabetes have been proven beneficial. The current study aims to investigate the effect of dietary modulation in the onset of diabetes and established the role of anti-diabetic NPs by using Drosophila melanogaster as a model system. The first objective aims to investigate the effects of dietary advanced glycated end products (AGE). Oral feeding of three types of AGE compounds (i.e. AGE glucose, AGE-fructose and AGE-ribose) was found to alter growth and development of the flies. Beside this, the larva and adults showed persistent hyperglycemic condition, excess fat deposition and micronuclei formation in gut and fat body as well as insulin resistance. The flies also showed increased ROS formation via downregulation of the antioxidant enzyme system. Behavioral defects were also evidenced in the larval and adult locomotion, suggesting neuronal damage. The second objective depicts the role of Strontium ferrite, a metallic nanoparticle as a non-toxic anti-diabetic agent. Files fed with a high fat diet (HFD) were used as a diabetic model. The toxicity profile of the nanoparticles was checked, showing no DNA damage or cytotoxicity. Feeding of the NPs to the diabetic flies demonstrated that, the NPs were able to reduce fly weight, metabolic sugar and triglyceride level, reduce the deposition of fat and also reduce ROS level and behavioral abnormalities. In the third objective, the flies were reared on a high sugar diet (HSD), which tremendously affected their growth and development. Beside this, behavioral alterations was also seen. Hyperglycemia followed by excess fat deposition in the gut, fat body and crop confirmed the diabetic phenotype. A novel polymeric nanoparticle, namely polyvinylpyrollidone-curcumin (PVP-C) was checked for antidiabetic potential. Non-cytotoxic and non-genotoxic potential of the nanoparticles were evidenced from no DNA damage, and absence of trypan blue staining, as well as no phenotypic abnormality. Treatment of PVP-C NPs to the diabetic flies showed reduction of metabolic contents and ROS level. Together the study suggests the role of diet in diabetic onset and importance of nanoparticles having potential to be used alone as an anti-diabetic agent or a combination to deliver therapeutic molecules.