title: Is the glucose-induced phosphate flush in pancreatic islets attributable to gating of volume-sensitive anion channels?
abstract: D-glucose and other nutrient insulin secretagogues have long been known to induce a transient increase in inorganic phosphate release from pancreatic islets, a phenomenon currently referred to as a "phosphate flush". The objective of this study was to explore the possible participation of volume-sensitive anion channels in such a process. Rat pancreatic islets were preincubated for 60 min in the presence of [32P]orthophosphate and then perifused for 90 min to measure 32P fractional outflow rate and insulin secretion. From minutes 46 to 70 inclusive either the concentration of D-glucose was increased from 1.1 to 8.3 mmol L-1 or the extracellular osmolarity was decreased by reducing the NaCl concentration by 50 mmol L-1. The increase in D-glucose concentration induced a typical phosphate flush and biphasic stimulation of insulin release. Extracellular hypoosmolarity caused a monophasic increase in both effluent radioactivity and insulin output. The inhibitor of volume-sensitive anion channels 5-nitro-2-(3-phenylpropylamino)benzoate (0.1 mmol L-1) inhibited both stimulation of insulin release and phosphate flush induced by either the increase in D-glucose concentration or extracellular hypoosmolarity. It is proposed that gating of volume-sensitive anion channels accounts for the occurrence of the phosphate flush and subsequent stimulation of insulin secretion in response to either an increase in D-glucose concentration or a decrease in extracellular osmolarity.
authors: Laboratory of Experimental Hormonology, Brussels Free University, 808 Route de Lennik, Brussels, 1070, Belgium.
authors: Karim
authors: K
authors: Louchami
authors: Ying
authors: Y
authors: Zhang
authors: Renaud
authors: R
authors: Beauwens
authors: Willy J
authors: WJ
authors: Malaisse
authors: Abdullah
authors: A
authors: Sener
mesh_terms: D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D051381:Rats
chemical_list: D007328:Insulin; D007473:Ion Channels; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D005947:Glucose
references: Diabetes. 2001 May;50(5):992-1003
references: 11334443
references: Exp Physiol. 1996 Nov;81(6):927-33
references: 8960699
references: Diabetologia. 1997 Jan;40(1):1-6
references: 9028711
references: Pflugers Arch. 1996 Jan;431(3):363-70
references: 8584429
references: J Physiol. 1997 Oct 1;504 ( Pt 1):191-8
references: 9350629
references: J Clin Invest. 1993 Feb;91(2):432-6
references: 8432852
references: Diabetologia. 1980 Nov;19(5):458-64
references: 7004965
references: J Physiol. 1978 Oct;283:409-24
references: 364009
references: Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1275-85
references: 11701444
references: Biochim Biophys Acta. 1979 Mar 22;583(3):370-7
references: 375990
references: Mol Cell Endocrinol. 2001 Jul 5;181(1-2):179-87
references: 11476951
references: J Clin Invest. 1974 Nov;54(5):1179-89
references: 4607816
references: Proc Natl Acad Sci U S A. 1976 Oct;73(10 ):3403-7
references: 790384