Physiological functions of glucose transporter-2: From cell physiology to links with diabetes mellitus

Glucose is a sugar crucial for human health since it participates in many biochemical reactions. It produces adenosine 5′-triphosphate (ATP) and nucleosides through glucose metabolic and pentose phosphate pathways. These processes require many transporter proteins to assist in transferring glucose across cells, and the most notable ones are glucose transporter-2 (GLUT-2) and sodium/glucose cotransporter 1 (SGLT1). Glucose enters small intestinal epithelial cells from the intestinal lumen by crossing the brush boundary membrane via the SGLT1 cotransporter. It exits the cells by traversing the basolateral membrane through the activity of the GLUT-2 transporter, supplying energy throughout the body. Dysregulation of these glucose transporters is involved in the pathogenesis of several metabolic diseases, such as diabetes. Natural loss of GLUT-2 or its downregulation causes abnormal blood glucose concentrations in the body, such as fasting hypoglycemia and glucose tolerance. Therefore, understanding GLUT-2 physiology is necessary for exploring the mechanisms of diabetes and targeted treatment development. This article reviews how the apical GLUT-2 transporter maintains normal physiological functions of the human body and the adaptive changes this transporter produces under pathological conditions such as diabetes.