Regulatory volume decrease of pancreatic beta-cells involving activation of tetraethylammonium-sensitive K+ conductance.
Beta-cell-rich pancreatic islets from ob/ob-mice were used for evaluating the early effects of hypotonic stress. The beta-cells responded to an abrupt lowering of the osmotic pressure by 102 mOsm with both a transient stimulation of insulin release (peak value 25 times above basal) and a loss of potassium without major effects on sodium. The secretory response was obtained also in the presence of 100 microM quinine or 20 mM tetraethylammonium+. The loss of potassium was not affected by 20 mM glucose or 10 microM bumetanide, but became less apparent in the presence of 100 microM quinine and disappeared when the islets were exposed to 20 mM tetraethylammonium+. Amiloride and high concentrations of the hypoglycemic sulfonylureas tolbutamide and glibenclamide had only a slight suppressive action on potassium mobilization. Patch clamp analyses revealed an increased frequency of small channel openings after exposure to the hypotonic medium. It is concluded that the pancreatic beta-cells have the ability for a regulatory volume decrease involving activation of tetraethylammonium-sensitive K+ conductance. The stimulation of insulin release obtained by lowering the osmotic pressure seems to be related to the entry of water rather than to the ion movements responsible for the readjustment of the beta-cell volume.
Marcström
A
A
Department of Medical Cell Biology, University of Uppsala, Sweden.
Lund
P E
PE
Hellman
B
B
D000818:Animals; D001711:Biotransformation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007038:Hypotonic Solutions; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D009997:Osmotic Pressure; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D007038:Hypotonic Solutions; D007328:Insulin; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D012964:Sodium; D005947:Glucose