Targeting Glycoproteins as a therapeutic strategy for diabetes mellitus and its complications

Abstract

Objectives Glycoproteins are organic compounds formed from proteins and carbohydrates, which are found in many parts of the living systems including the cell membranes. Furthermore, impaired metabolism of glycoprotein components plays the main role in the pathogenesis of diabetes mellitus. The aim of this study is to investigate the influence of glycoprotein levels in the treatment of diabetes mellitus. Methods All relevant papers in the English language were compiled by searching electronic databases, including Scopus, PubMed and Cochrane library. The keywords of glycoprotein, diabetes mellitus, glycan, glycosylation, and inhibitor were searched until January 2019. Results Glycoproteins are pivotal elements in the regulation of cell proliferation, growth, maturation and signaling pathways. Moreover, they are involved in drug binding, drug transportation, efflux of chemicals and stability of therapeutic proteins. These functions, structure, composition, linkages, biosynthesis, significance and biological effects are discussed as related to their use as a therapeutic strategy for the treatment of diabetes mellitus and its complications. Conclusions The findings revealed several chemical and natural compounds have significant beneficial effects on glycoprotein metabolism. The comprehension of glycoprotein structure and functions are very essential and inevitable to enhance the knowledge of glycoengineering for glycoprotein-based therapeutics as may be required for the treatment of diabetes mellitus and its associated complications.

Altered O-glycomes of Renal Brush-Border Membrane in Model Rats with Chronic Kidney Diseases

“…For example, O -glycans without sialic acids and fucoses were barely found in the obese and diabetic group. It has been reported that the process of the Mucin type glycosylation formation is catalyzed by N -acetylgalactosaminyl transferases (GalNAc-transferases) from a family of uridine diphosphate- N -acetylgalactosamine [ 61 ]. A lack of expression or low expression of certain O -glycans may be related to the activity of GalNAc-transferases, which could possibly be influenced by the obese and diabetic symptoms.…”

Sweetening the Deal: Glycosylation and its Clinical Applications

“…As previously mentioned, efforts have been made to conjugate existing and new pharmaceuticals to various glycans to enhance stability, safety and clinical efficacy [8]. Differential glycosylation is being profiled in diseases to be developed as novel vaccine or drug targets [25]. Attempts have been made to change glycosylation patterns of immune components to boost the body's inherent strength to fight infection and diseases [27].…”

“…See Figure 2 for a diagram depicting this mechanism. Aside from tumours, glycoprotein pattern recognition has also been studied for its potential use in treating diabetes mellitus and its long-term complications [25]. The abnormal metabolism of glycoproteins and its derivatives contributes greatly to the pathogenesis and progression of diabetes.…”

Supercritical-CO2 extraction, identification and quantification of polyprenol as a bioactive ingredient from Irish trees species

“…In the human body polyprenols are metabolised into dolichols and dolichyl phosphate by enzymatic catalysis 11 . In humans, dolichols regulate the permeability and stability of membranes, partaking in the biosynthesis of human glycoproteins 11 , 12 . Both dolichols and polyprenols are found in the form of esters, carboxylic acids and free alcohol in the cell 13 , while a small portion is found in the form of phosphates 14 .…”