Regulation of glucose uptake in differentiated cells

Glucose uptake into the cell is mediated by a family of glycosylated membrane proteins, called glucose transporters (GTs) that are able to facilitate passive hexose transfer across the lipid plasma membrane. The tissue-specific transporter isoforms generally differ in their affinity to the natural substrate D-glucose according to the specific functions of the respective organ. The mechanisms by which external and internal signals regulate glucose uptake into the cells belong to one of the most extensively studied fields of cell physiology. However, in spite of significant progress in identifying the involved molecular components and signaling pathways, the final cellular mechanism responsible for the short-term regulation of glucose uptake is still a matter of intense debate. The widely accepted translocation hypothesis, which explains transport regulation by exo- and endocytic modulation of the number of GTs in the plasma membrane, insufficiently accounts for the whole insulin-induced transport stimulation and is insufficient to integrate the wide variety of different transport-modulating signals in differentiated tissue cells into a common mechanistic concept. Some time ago, a novel type of glucose transport regulation has been proposed prevailing in differentiated tissue cells. This mechanism depends on the presence of glucose transporters on microvilli of differentiated cells. The basic framework for this theory was provided by a recently presented novel concept of ion channel regulation via microvillar structures [Lange, K. (1999): Microvillar Ca++ signaling: A new view on an old problem. J. Cell. Physiol. 180, 19-35; Lange, K. (2000): Regulation of cell volume via microvillar ion channels. J. Cell. Physiol. 185, 21-35; Lange, K. (2000): Microvillar ion channels Cytoskeletal regulation of ion fluxes. J. Theor. Biol. 206, 561-584], earlier studies on glucose transport regulation and a number actual biochemical findings. Here, a survey on both concepts is given and the ability of the novel mechanism of microvillar transport regulation to integrate a large body of experimental data into the common concept of cellular regulation via microvillar pathways is discussed.