RECENT ADVANCES IN TARGETING PROTEINS AND ENZYMES ASSOCIATED WITH DIABETIC PATHOPHYSIOLOGY

Abstract

Background: Diabetes mellitus is a multifactorial metabolic disorder involving several pathways, i.e., enzymes and proteins, and is a major causing morbidity and mortality worldwide. Its complex nature makes it a target for multiple therapeutic approaches, each addressing specific dysfunctions to achieve glycemic control and reduce complications. Objectives: The present review explores the different proteins, pathways, and enzymes involved in diabetic pathophysiology, including their metabolic roles and properties as targets of modulations by antidiabetic agents. Methodology: A literature review was conducted via different major electronic databases, including Google Scholar, PubMed, Ovid, EMBASE, and MEDLINE, to retrieve relevant literature. Results: Some of the significant dysfunctions include insulin absence and resistance, glucose toxicity, dyslipidemia, nephropathy, retinopathy, neuropathy, and cardiovascular complications, which are mostly attributed to persistent hyperglycemia. Moreover, different proteins and enzymes are associated with diabetic pathophysiology, including 11β-hydroxysteroid dehydrogenase, glutamine: fructose-6-phosphate aminotransferase, alpha-glucosidase, glucokinase, glucose-6-phosphate dehydrogenase, protein tyrosine phosphatase 1B, renin-Angiotensin-aldosterone-system, mono-ADP ribosyltransferase-sirtuin-6, and pyruvate dehydrogenase complex which acts as modulative targets of antidiabetic agents to manage diabetes. Conclusion: The diabetic pathology is attributed to glucotoxicity and dyslipidemia caused by persistent hyperglycemia. Modulating these pathways, proteins, and enzymes could play significant roles in diabetes management. Furthermore, novel antidiabetic therapeutics from different pharmaceutical sources might be developed by exploring these pathways.