Volume regulation in mouse pancreatic beta-cells is mediated by a furosemide-sensitive mechanism.
A possible role for loop diuretic-sensitive Cl-/cation cotransport in volume regulation in the pancreatic beta-cells was investigated by measuring 86Rb+ efflux from beta-cell-rich pancreatic islets as well as the size of isolated beta-cells under different osmotic conditions. Lowering the osmolarity to 262 mosM (83% of control) resulted in a rapid cell swelling which was followed by regulatory volume decrease (RVD). RVD was completely inhibited by furosemide (1 mM), an inhibitor of Cl-/cation co-transport. The hypotonic medium (262 mosM) induced a rapid and strong increase in 86Rb+ efflux from beta-cell-rich mouse pancreatic islets and the furosemide-sensitive portion of the efflux was significantly increased. A slightly less hypotonic medium (285 mosM, 90% of control) induced only cell swelling and no RVD. With this medium only a marginal increase in 86Rb+ efflux was observed. Increasing the osmolarity by adding 50 mM NaCl (final osmolarity: 417 mosM, 132% of control) induced a rapid cell shrinkage but no regulatory volume increase (RVI). When the osmolarity was increased from a slightly hypotonic medium (262 mosM) to an isotonic medium (317 mosM) an initial cell shrinkage was followed by RVI. This RVI was inhibited by 1 mM furosemide. The data suggest that RVD as well as RVI in the beta-cells are mediated by loop diuretic-sensitive cotransport of chloride and cations and that these cells show a threshold for hypotonic stimulation of RVD.
Engström
K G
KG
Department of Histology and Cell Biology, University of Umeå.
Sandström
P E
PE
Sehlin
J
J
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D003470:Culture Media; D005665:Furosemide / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007552:Isotonic Solutions; D051379:Mice; D009994:Osmolar Concentration; D012414:Rubidium Radioisotopes; D012965:Sodium Chloride
D003470:Culture Media; D007552:Isotonic Solutions; D012414:Rubidium Radioisotopes; D012965:Sodium Chloride; D005665:Furosemide