Glucose‐induced swelling in rat pancreatic β‐cells

Abstract

Changes in relative cell volume in response to hypotonic solutions and glucose were studied in single isolated rat pancreatic β‐cells using a video‐imaging technique, β‐cell electrical activity was recorded under similar conditions using the perforated patch technique. Exposure of β‐cells to hypotonic solutions (10 and 33% hypotonicity) 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. Raising the concentration of glucose from 4 to 20 mm or 12 mm (with substitution of mannitol) increased β‐cell volume by 12 and 10%, respectively. This effect of glucose persisted when Co2+ was added to inhibit insulin release. Glucose‐induced volume increases were sustained for the duration of exposure to elevated hexose concentration. The addition of 16 mm 3‐O‐methylglucose, which is transported into the β‐cell but not metabolized, produced only a transient 5% increase in β‐cell volume. Exposure of β‐cells to a 15% hypotonic solution resulted in a transient depolarization and electrical activity. Raising the glucose concentration to 20 or 12 mm caused a sustained depolarization and generation of electrical activity. However, the addition of 16 mm 3‐O‐methylglucose had no effect on β‐cell membrane potential. The glucose‐induced increase in volume and induction of electrical activity, when measured in single β‐cells simultaneously, showed comparable kinetics. The secretion of insulin from intact pancreatic islets was stimulated by exposure to hypotonic solutions (10–33% hypotonicity). A 15% hypotonic solution stimulated insulin release to a peak value comparable to that elicited by raising the glucose concentration from 4 to 20 mm. Whereas hypotonic solutions caused a transient stimulation of insulin release, the effect of glucose was sustained. It is suggested that glucose increases the volume in rat pancreatic β‐cells by a mechanism dependent upon metabolism of the sugar. The extent of cell swelling evoked by raised glucose concentrations is sufficient to depolarize the cells and induce electrical and secretory activity and may involve activation of a volume‐sensitive anion conductance.

Effects of octane derivatives on activity of the volume-regulated anion channel in rat pancreatic β-cells

“…Relative cell volume was measured using a videoimaging technique [5,9]. b-Cells were superfused with the isotonic (291 ± 1 mosmol/Kg H 2 O) bath solution containing 4 mM/l glucose.…”

The role of thermosensitive TRP (transient receptor potential) channels in insulin secretion [Review]

“…This [Ca 2+ ] i increase causes ER stress and impaired cell viability [9]. Although there is little evidence for TRPV4 involvement in insulin secretion, [Ca 2+ ] i increases in β-cells may occur through TRPV4 activation caused by cell volume changes upon glucose uptake [46,47].…”

Chloride Channels Regulate HIT Cell Volume but Cannot Fully Account for Swelling-Induced Insulin Secretion

“…I Cl,islet is inhibited by the well-known Cl Ϫ channel blocker 4,4Ј-diisothiocyanatostilbene-2,2Ј-disulfonic acid (DIDS) or by 100 mol/l glyburide (5). The channel may also be under metabolic control, either by virtue of its sensitivity to intracellular ATP (5,6) or because of ␤-cell swelling associated with increased glucose metabolism (7).…”