Effect of exogenous ATP upon inositol phosphate production, cationic fluxes and insulin release in pancreatic islet cells.
Endogenous ATP is thought to play a key regulatory role in nutrient-stimulated insulin release. The present study deals with the effect of exogenous ATP and its stable analog alpha, beta-methylene ATP upon pancreatic islet function. Both alpha, beta-methylene ATP (5.0 microM to 0.2 mM) and ATP (0.3-3.0 mM) caused a rapid and concentration-related increase in insulin output by rat islets incubated or perfused at an intermediate concentration of D-glucose (8.3 mM). The effect of the ATP analog faded out at both lower and higher D-glucose concentrations. In the presence of 8.3 mM D-glucose, ATP also increased both 86Rb and 45Ca outflow from prelabelled islets. The cationic response to ATP persisted in the absence of extracellular Ca2+ and, hence, was reminiscent of that evoked by cholinergic agents. Like carbamylcholine, ATP caused a dose-related increase in the production of [3H]inositol phosphates from prelabelled islets or tumoral islet cells (RINm5F line). The latter effect was duplicated by alpha, beta-methylene ATP and unaffected by atropine. It is speculated that ATP, liberated together with insulin at the exocytotic site, might participate in a positive feedback control of insulin release.
Blachier
F
F
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Malaisse
W J
WJ
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002132:Calcium Radioisotopes / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007328:Insulin / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000096:biosynthesis; D051381:Rats; D012414:Rubidium Radioisotopes / Q000378:metabolism; D013403:Sugar Phosphates / Q000096:biosynthesis*
D002132:Calcium Radioisotopes; D007295:Inositol Phosphates; D007328:Insulin; D007473:Ion Channels; D010716:Phosphatidylinositols; D012414:Rubidium Radioisotopes; D013403:Sugar Phosphates; D000255:Adenosine Triphosphate; D005947:Glucose