Pancreatic β-cells increase in volume when exposed to elevated concentrations of extracellular glucose. This study has examined the effects of glucose on the volumes of pancreatic α-cells, which like β-cells are regulated by glucose, and intestinal epithelial Caco-2 cells which are unresponsive to glucose. Cell volume changes were monitored by a video-imaging method. Increasing the extracellular glucose concentration caused a concentration-dependent increase in α-cell volume over the range 1–20mM. Glucose-induced swelling was not, however, observed in Caco-2 cells. The glucose-induced swelling in both α- and β-cells was abolished by 0.5mM phloretin, an inhibitor of the GLUT proteins, indicating that GLUT mediated glucose transport is a pre-requisite for swelling. Glucose metabolism also appears to be essential, as islet cell swelling was not observed with 16mM 3-O-methyl glucose. These data suggest that glucose-induced swelling may be a property exclusive to glucose-regulated cells.