Contrasting effects of glycerol and urea transport on rat pancreatic beta-cell function.
OBJECTIVE
Pancreatic beta-cell function is influenced by changes in cell volume. Such volume changes depend on water permeability of the plasma membrane, conferred in part by aquaporins. Islet cells express aquaporin 7 (AQP7), which is permeable to urea and glycerol in addition to water. We therefore investigated the effects of glycerol and urea on rat pancreatic beta-cell function.


METHODS
Electrical activity and whole-cell current were studied using the perforated patch technique. Cell volume was measured by video-imaging and insulin release by radioimmunoassay. Aquaporin 7 expression was studied by RT-PCR, Western blot and double fluorescent immunolabelling.


RESULTS
The isosmotic addition of glycerol and urea resulted in depolarization of the plasma membrane and electrical activity, accompanied by beta-cell swelling, activation of the volume-regulated anion channel (VRAC) and insulin release. However, the effects of glycerol, in contrast to urea, persisted throughout exposure to the osmolyte. Glycerol also caused beta-cell activation when added hyperosmotically. A non-metabolizable glycerol analogue had comparable effects to urea on beta-cells. The expression of AQP7 was demonstrated in rat beta-cells.


CONCLUSIONS
Glycerol and urea can activate beta-cells via their rapid uptake across the beta-cell plasma membrane, possibly via AQP7. This results in cell swelling, VRAC activation, electrical activity and insulin release. Glycerol appears to exert an additional effect, possibly related to its intracellular metabolism.
Best
Leonard
L
Faculty of Medicine, University of Manchester, UK.
Brown
Peter D
PD
Yates
Allen P
AP
Perret
Jason
J
Virreira
Myrna
M
Beauwens
Renaud
R
Malaisse
Willy J
WJ
Sener
Abdullah
A
Delporte
Christine
C
D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D016764:Cell Polarity; D005990:Glycerol / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000502:physiology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D014508:Urea / Q000378:metabolism* / Q000494:pharmacology; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism
C491926:Aqp7 protein, rat; D020346:Aquaporins; D007328:Insulin; D050994:Voltage-Dependent Anion Channels; D014508:Urea; D005990:Glycerol