Pathophysiology of Glut2 in Diabetes Mellitus

Abstract

Glucose is a polar molecule and its transport through biological membranes requires the presence of specific transporter proteins. Five structurally related hexose carriers have been described that facilitate the diffusion of glucose and closely related hexoses through the cell membrane. These proteins, referred to as GLUT1 to GLUTS, are the products of different genes located on different chromosomes and are functionally distinguished by their hexose specificity, affinity for glucose, tissue and cellular localization and regulated expression in different metabolic states and in response to different hormones (1,2). GLUT1, GLUTS and GLUT4, are high affinity glucose transporters (Km for glucose of 1-5 mM), GLUTS is mostly a fructose transporter and GLUT2 has a uniquely low affinity for glucose (Km for glucose ∼17 mM) (3). This transporter is expressed selectively in tissues in which high glucose fluxes are required. In intestine, it is found in the basolateral membrane of epithelial cells and is thought to be responsible for the second step of transepithelial glucose uptake. A similar role for GLUT2 is anticipated in glucose reabsorption in the proximal convoluted tubule where it is located to the basolateral membrane of epithelial cells. GLUT2 is also expressed at a high level in the sinusoidal membrane of hepatocytes where the transporter may function both for glucose uptake and release from the cells. In pancreatic [3-cells, GLUT2 may be part of a glucose sensing system-linking variations in plasma glucose to insulin secretion (4).