Zebrafish: A Model to Study and Understand the Diabetic Nephropathy and Other Microvascular Complications of Type 2 Diabetes Mellitus

Abstract

Diabetes mellitus (DM) is a complicated metabolic illness that has had a worldwide impact and placed an unsustainable load on both developed and developing countries’ health care systems. According to the International Diabetes Federation, roughly 537 million individuals had diabetes in 2021, with type 2 diabetes mellitus accounting for the majority of cases (T2DM). T2DM is a chronic illness defined by insufficient insulin production from pancreatic islet cells. T2DM generates various micro and macrovascular problems, with diabetic nephropathy (DN) being one of the most serious microvascular consequences, and which can lead to end-stage renal disease. The zebrafish (Danio rerio) has set the way for its future as a disease model organism. As numerous essential developmental processes, such as glucose metabolism and reactive metabolite production pathways, have been identified in zebrafish that are comparable to those seen in humans, it is a good model for studying diabetes and its consequences. It also has many benefits over other vertebrate models, including the permeability of its embryos to small compounds, disease-driven therapeutic target selection, in vivo validation, and deconstruction of biological networks. The organism can also be utilized to investigate and understand the genetic abnormalities linked to the onset of diabetes problems. Zebrafish may be used to examine and visualize the growth, morphology, and function of organs under normal physiological and diabetic settings. The zebrafish has become one of the most useful models for studying DN, especially when combined with genetic alterations and/or mutant or transgenic fish lines. The significant advancements of CRISPR and next-generation sequencing technology for disease modelling in zebrafish, as well as developments in molecular and nano technologies, have advanced the understanding of the molecular mechanisms of several human diseases, including DN. In this review, we emphasize the physiological and pathological processes relating to microvascular problems in zebrafish, as well as the many experimental zebrafish models used to research DN, and the DN-related outcomes and mechanisms observed in zebrafish.

Urinary insulin signaling pathway related proteins may serve as potential biomarkers for monitoring diabetes mellitus without hypertension and hyperlipidemia

“…PRKAR2A is a major regulatory subunit of cyclic AMP dependent protein kinases that catalyzes downstream substrate protein phosphorylation by detecting cyclic AMP signaling. [19][20][21][22][23][24] It is essential for β-cell differentiation and insulin secretion, and is involved in the regulation of lipid and glucose metabolism. [25][26][27] Growth factor receptor binding protein 2 (GRB2) is a widely studied bridging protein involved in cell signaling.…”

Retinol Binding Protein 4 as a Recent Biomarker for Prediction of Diabetic Nephropathy in Type 2 Diabetic Patients

“…Diabetic nephropathy is a common and serious complication of DM and is one of the leading causes of end-stage renal disease worldwide [5]. It is also associated with cardiovascular causes of mortality.…”

A Collection Of Novel Techniques to Study Diabetes and Obesity

“…Changes in memory and/or cognitive impairment are among the concerning effects of uncontrolled hyperglycemia in patients with elevated blood glucose. As zebrafish have successfully been used in studies testing the effects of altered glucose homeostasis 13 , this organism should now be used in behavioral studies as well. In their second article, Rowe et al demonstrate a method to use zebrafish in behavioral studies 14 using a modified three-chambered apparatus designed to monitor social interactions in the mouse 15 .…”