Plasma membrane associated ATP as a regulator of the secretory activity of the pancreatic beta-cell.
beta-Cell-rich pancreatic islets from ob/ob-mice were used for evaluating how ATP associated with the plasma membrane participates in the regulation of insulin release. Increase of Ca2+ initiates insulin release from permeabilized beta-cells only in the presence of Mg-ATP. When bound to the inner part of the plasma membrane ATP depolarizes the beta-cells by closing a glucose-regulated K+-channel. It is possible that ATP in a plasma membrane compartment modulates insulin release also by stimulating ion pumps and exchange processes. ATP can regulate the secretory activity by binding also to the exterior of the beta-cells. The addition of ATP resulted in stimulation of insulin release related to polyphosphoinositide breakdown. It is suggested that the granule fusion with the plasma membrane is followed by release of sufficient amounts of ATP and ADP for activating a P2-purinoceptor. This receptor may consequently be part of a system for amplifying the secretory response to glucose and other agents facilitating the entry of Ca2+.
Hellman
B
B
Department of Medical Cell Biology, University of Uppsala, Sweden.
Gylfe
E
E
Wesslén
N
N
Hallberg
A
A
Grapengiesser
E
E
Marcström
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003593:Cytoplasm / Q000032:analysis; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000032:analysis / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D007328:Insulin; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D005947:Glucose; D002118:Calcium