High sucrose diet induces morphological, structural and functional impairments in the renal tubules of Drosophila melanogaster: A model for studying type-2 diabetes mediated renal tubular dysfunction.

Abstract

Continuous feeding of high dietary sugar is strongly associated with type 2 diabetes (T2D) and its secondary complications. Diabetic nephropathy (DN) is a major secondary complication that leads to glomerular and renal tubular dysfunction. The present study is aimed to investigate the effects of chronic exposure of high sugar diet (HSD) on renal tubules. Malpighian tubules (MTs), a renal organ of Drosophila, were used as a model in the study. Feeding of HSD develops T2D condition in Drosophila. The MTs showed structural abnormalities in 20 days of HSD fed flies. Impaired insulin signaling, oxidative stress, enhanced levels of AGE-RAGE and induction of apoptosis were observed in the MTs of these flies. Further, altered expression of transporters, enhanced uric acid level and reduced fluid secretion rate confirmed the impaired function of MTs in these flies. RNA-seq and RT-PCR analyses in the MTs of HSD fed-and control-flies revealed the altered expression of candidate genes that regulate several important pathways including extracellular matrix (ECM), advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), transforming growth factor β (TGF-β), galactose, starch and sucrose metabolism that are well known mediators of renal tubular dysfunction in DN patients. Disruption of insulin signaling in the MTs also causes renal tubular dysfunction similar to HSD fed flies. Overall, the study suggests that phenotypes observed in the MTs of HSD fed flies recapitulate several hallmarks of renal tubular dysfunction in DN patients. Therefore, we conclude that MTs of HSD fed flies may be used for deciphering the underlying mechanisms of T2D mediated renal tubular dysfunction.

• Authors: Lavi Rani, Sanjay Saini, Neha Shukla, Debapratim Kar Chowdhuri, Naveen Kumar Gautam
• Journal: Insect biochemistry and molecular biology (Insect Biochem Mol Biol) Vol. 125 Pg. 103441 (10 2020) ISSN: 1879-0240 [Electronic] England
• PMID: 32735915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Dietary Sucrose
• Glycation End Products, Advanced
• Insulin
• Transforming Growth Factor beta

Topics

• Animals
• Apoptosis
• Diabetes Mellitus, Type 2 (physiopathology)
• Diabetic Nephropathies (physiopathology)
• Dietary Sucrose (metabolism)
• Disease Models, Animal
• Drosophila melanogaster (physiology)
• Glycation End Products, Advanced (metabolism)
• Insulin (metabolism)
• Malpighian Tubules (physiopathology)
• Oxidative Stress
• Signal Transduction
• Transforming Growth Factor beta (metabolism)