Secretory phospholipase A2 is released from pancreatic beta-cells and stimulates insulin secretion via inhibition of ATP-dependent K+ channels.
The release of sPLA(2) from single mouse pancreatic beta-cells was monitored using a fluorescent substrate of the enzyme incorporated in the outer leaflet of the plasma membrane. Stimulation of beta-cells with agents that increased cytosolic free Ca(2+) concentration ([Ca(2+)](i)) induced a rapid release of sPLA(2) to the extracellular medium. Exogenous sPLA(2) strongly stimulated insulin secretion in mouse pancreatic islets at both basal and elevated glucose concentrations. The stimulation of insulin secretion by sPLA(2) was mediated via inhibition of ATP-dependent K(+) channels and an increase in [Ca(2+)](i). Measurements of cell capacitance in single beta-cells revealed that sPLA(2) did not modify depolarisation-induced exocytosis. Our data suggest that a positive feedback regulation of insulin secretion by co-released sPLA(2) is operational in pancreatic beta-cells and point to this enzyme as an autocrine regulator of insulin secretion.
Juhl
Kirstine
K
Laboratory of Islet Cell Physiology, Novo Nordisk A/S, Novo Alle, DK-2880 Bagsvaerd, Denmark.
Efanov
Alexander M
AM
Olsen
Hervør L
HL
Gromada
Jesper
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005089:Exocytosis; D005260:Female; D054500:Group IB Phospholipases A2; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism* / Q000502:physiology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D051379:Mice; D018408:Patch-Clamp Techniques; D010741:Phospholipases A / Q000378:metabolism* / Q000494:pharmacology*; D054467:Phospholipases A2; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D007328:Insulin; D008244:Lysophosphatidylcholines; D026902:Potassium Channel Blockers; D016718:Arachidonic Acid; D000255:Adenosine Triphosphate; D010741:Phospholipases A; D054500:Group IB Phospholipases A2; D054467:Phospholipases A2; C516203:Pla2g1b protein, mouse; D002118:Calcium