Are ionic fluxes of pancreatic beta cells a target for gastric inhibitory polypeptide?
Gastric inhibitory polypeptide (GIP), an incretin candidate, is suggested to amplify the glucose-induced insulin secretion. To evaluate its mode of action we examined whether GIP affects 86Rb+ efflux, 45Ca2+ uptake or efflux, and intracellularly recorded electrical activity of mouse pancreatic islets. GIP (5 nM) neither inhibited 86Rb+ efflux at 3 mM glucose nor modulated 86Rb+ efflux that was inhibited by 5.6 mM glucose or stimulated by the calcium ionophore A23187. 45Ca2+ uptake was increased by GIP in the presence of 16.7 mM which was not observed at 3 or 11 mM glucose. GIP elevated 45Ca2+ efflux from islets, but did not modify 45Ca2+ efflux when a virtually Ca2+ free medium was used. Electrical activity of beta cells induced by 16.7 mM glucose was significantly increased by 5 nM GIP. It is concluded that the amplification of insulin release by GIP is based on the effect of GIP on Ca2+ uptake.
Wahl
M A
MA
Department of Pharmacology, Eberhard-Karls Universität Tübingen, Germany.
Plehn
R J
RJ
Landsbeck
E A
EA
Verspohl
E J
EJ
Ammon
H P
HP
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D012413:Rubidium / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects; D013268:Stimulation, Chemical
D007328:Insulin; D007473:Ion Channels; D005749:Gastric Inhibitory Polypeptide; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D005947:Glucose; D012413:Rubidium; D002118:Calcium