GLUCOSE-INDUCED SWELLING IN RAT PANCREATIC BETA-CELLS

1. Changes in relative cell volume in response to hypotonic solutions and glucose were studied in single isolated rat pancreatic beta-cells using a video-imaging technique. beta-cell electrical activity was rec orded under similar conditions using the perforated patch technique. 2 . Exposure of beta-cells to hypotonic solutions (10 and 33% hypotonici ty) caused an immediate increase in cell volume to relative values of 1.09 and 1.33, respectively. This was followed by a gradual regulatory volume decrease. 3. Raising the concentration oi. glucose from 4 to 2 0 mM or 12 mM (with substitution of mannitol) increased beta-cell volu me by 12 and 10%, respectively. This effect of glucose persisted when Co2+ nas added to inhibit insulin release. Glucose-induced volume incr eases were sustained for the duration of. exposure to elevated hexose concentration. The addition of 16 mM 3-O-methylglucose, which Is trans ported into the beta-cell but not metabolized, produced only a transie nt 5% increase in beta-cell volume. 4. Exposure of beta-cells to a 15% hypotonic solution resulted in a transient depolarization and electri cal activity. Raising the glucose concentration to 20 or 12 mM caused a sustained depolarization and generation of electrical activity. Howe ver, the addition of 16 mM 3-O-methylglucose had no effect on beta-cel l membrane potential. The glucose-induced increase in volume and induc tion of electrical activity, when measured in single beta-cells simult aneously, showed comparable kinetics. 5. The secretion of insulin from intact pancreatic islets was stimulated by exposure to hypotonic solu tions (10-33 % hypotonicity). A 15% hypotonic solution stimulated insu lin release to a peak value comparable to that elicited by raising the glucose concentration from 4 to 20 mM. Whereas hypotonic solutions ca used a transient stimulation of insulin release, the effect of glucose was sustained. 6. It is suggested that glucose increases the volume i n rat pancreatic beta-cells bu a mechanism dependent upon metabolism o i the suer. The extent of cell swelling evoked by raised glucose conce ntrations is sufficient to depolarize the cells and induce electrical and secretory activity and may involve activation of a volume sensitiv e anion conductance.