Glucose transporters in health and disease: from molecular mechanisms to therapeutic applications

The purpose of this review is to provide a comprehensive analysis of glucose transporters, integrating molecular mechanisms, physiological roles, and therapeutic applications across health and disease states. Glucose transport across cellular membranes, mediated by facilitative glucose transporters (GLUTs) and sodium-glucose cotransporters (SGLTs), represents a fundamental control point in glucose homeostasis. Since the initial discovery of specific membrane components for glucose transfer in 1948, our understanding has evolved substantially, revealing complex tissue-specific expression patterns and regulatory mechanisms. Recent structural biology advances, genetic studies, and clinical developments, particularly the success of SGLT2 inhibitors in treating type 2 diabetes and their unexpected benefits in heart failure and chronic kidney disease, have transformed our understanding of these essential proteins. This review examines the structural and functional properties of glucose transporters, their tissue-specific distribution and regulation, their roles in metabolic organs, and their dysfunction in various diseases. We specifically address unresolved questions regarding tissue-specific regulation, expanding roles in disease pathogenesis beyond diabetes, and emerging therapeutic strategies. By synthesizing recent technological advances, clinical implications, and areas of continuing controversy, this review provides a framework for understanding both the fundamental biology of glucose transporters and their growing therapeutic significance in metabolic diseases.